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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Vitamin D &#40;VD&#41; is a prohormone obtained mainly from exposure to ultraviolet B &#40;UVB&#41; radiation and diet &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> VD plays an essential role in bone health and immunity&#46; Furthermore&#44; VD has an antineoplastic effect by regulating cell proliferation&#44; differentiation&#44; migration&#44; and apoptosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">2&#44;3</span></a> VD has been associated with a lower risk of colorectal&#44; breast&#44; and prostate cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">4</span></a> However&#44; this association is controversial in the case of skin cancer &#40;SC&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#44;6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Since 2009&#44; 25-hydroxyvitamin D or colecalciferol &#40;25VD&#41; has been quantified to recognize VD levels&#46; According to the National Academy of Medicine &#40;NAM&#41;&#44; 25VD levels &#62;<span class="elsevierStyleHsp" style=""></span>20 ng&#47;mL are sufficient for optimal health&#44; while the American Endocrine Society &#40;AES&#41; suggests levels &#62;<span class="elsevierStyleHsp" style=""></span>30 ng&#47;mL&#59; insufficient levels range between 20 ng&#47;mL and 30 ng&#47;mL&#44; and deficient levels are those &#60;<span class="elsevierStyleHsp" style=""></span>20 ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a> In recent years&#44; VD deficiency and insufficiency have been regarded as having &#8220;pandemic proportions&#46;&#8221; Up to 70&#37; of the European population may have insufficient levels&#44; even in countries with high sun exposure&#44; such as Mediterranean regions&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">7</span></a> Some authors attribute this phenomenon to reduced sunlight exposure and&#47;or diets low in VD-rich foods&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a> However&#44; other authors consider the cutoff of 20 ng&#47;mL or 30 ng&#47;mL too high&#44; which would explain why most of the European population has low VD levels without accompanying symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a> Recently&#44; considering the contradictory evidence on the utility of measuring and supplementing VD&#44; the U&#46;S&#46; Preventive Services Task Force has ill-advised measuring and supplementing VD levels in healthy individuals&#44; something that should only be done in patients at risk of osteoporosis or fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">As previously noted&#44; the relationship between VD and SC is controversial&#44; and the evidence is often contradictory&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#44;6</span></a> In this article&#44; we will be reviewing the association between VD and the development and prognosis of SC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We conducted a narrative review of currently available literature&#46; Searches were conducted in Spanish and English across Medline and Google Scholar from September through October 2023 using the terms &#8220;vitamin D&#44;&#8221; &#8220;calcitriol&#44;&#8221; &#8220;colecalciferol&#44;&#8221; &#8220;skin cancer&#44;&#8221; &#8220;melanoma&#44;&#8221; &#8220;squamous cell carcinoma&#44;&#8221; &#8220;basal cell carcinoma&#44;&#8221; &#8220;immunotherapy&#44;&#8221; &#8220;supplementation&#44;&#8221; &#8220;response to targeted therapy&#44;&#8221; and &#8220;response to immunotherapy&#46;&#8221; The search included articles from January 1<span class="elsevierStyleSup">st</span>&#44; 2000 through September 1<span class="elsevierStyleSup">st</span>&#44; 2023&#46; Prospective and retrospective studies with &#8805; 10 patients&#44; and systematic reviews &#40;SRs&#41; and meta-analyses &#40;MAs&#41;&#44; were included&#46; Articles were screened based on their abstracts and selected based on their relevance&#46; Two authors &#40;MMP and DMC&#41; conducted the search and selected the articles&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">A&#46; Vitamin D and non-melanoma skin cancer</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Development of non-melanoma skin cancer</span><p id="par0025" class="elsevierStylePara elsevierViewall">Multiple studies have tried to elucidate the relationship between 25VD levels or VD supplementation and non-melanoma skin cancer &#40;NMSC&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#44;10&#8211;22</span></a> Most found that sufficient VD levels &#40;&#8805; 20 ng&#47;mL or &#8805; 30 ng&#47;mL depending on the studies&#41; were associated with a higher risk of NMSC&#44; especially basal cell carcinoma &#40;BCC&#41;&#46; Nonetheless&#44; two recent SRs have provided contradictory results&#46; Back in 2021&#44; Caini et al&#46; published 1 SR and 1 MA that included 24 studies&#58; 3 prospective and 21 retrospective &#40;58 067 patients overall&#41;&#46; They found a direct association between 25VD levels and the risk of NMSC&#44; and between a higher 25VD intake and the risk of NMSC&#46; This risk seemed more evident in observational studies than in clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a> However&#44; in 2022&#44; in a different SR that included 10 studies and 204 000 patients&#44; Abdelwahab et al&#46; stated that it could not be concluded that there was an actual relationship between 25VD levels and the occurrence of BCC&#46; They also said that this inconsistency was due to the lack of homogeneity of the included studies&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">22</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Effects of vitamin D supplementation on skin cancer</span><p id="par0030" class="elsevierStylePara elsevierViewall">A randomized placebo-controlled trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36 282&#41; evaluated the effects of supplementation with 400 IU of VD and 1000<span class="elsevierStyleHsp" style=""></span>mg of calcium on the risk of developing NMSC and melanoma in postmenopausal women&#46; The mean follow-up was 7 years&#46; Supplementation failed to reduce the overall incidence of NMSC or melanoma&#46; In a subanalysis&#44; the group of women with a history of NMSC who received supplementation had a lower risk of developing melanoma &#40;hazard ratio&#44; 0&#46;43&#59; 95&#37;CI&#44; 0&#46;21-0&#46;90&#41; compared with the placebo group&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> One MA from 2020 that included prospective studies only &#40;13 studies with&#44; overall&#44; more than 200 000 patients&#41; also failed to reveal a higher risk of cutaneous squamous cell carcinoma or melanoma but did show a higher risk of basal cell carcinomas in individuals who were on VD supplements&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">23</span></a> Similar results were observed in the SR conducted by Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">B&#46; Vitamin D and melanoma</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Development of melanoma</span><p id="par0035" class="elsevierStylePara elsevierViewall">Numerous studies have associated VD with the development or progression of melanoma &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">table 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;16&#44;17&#44;20&#44;24&#8211;44</span></a> Certain reports link lower levels of VD with a higher incidence of melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">33&#8211;35&#44;37&#44;44&#44;45</span></a> One 2023 SR and 1 MA&#44; which collected 14 case-control studies and prospective cohorts for a total of 6111 patients confirmed a higher incidence of melanoma and a higher Breslow thickness &#40;BT&#41; in patients with VD insufficiency &#40;&#8804; 30 ng&#47;mL&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a> However&#44; other studies have not found a relationship between VD levels and the incidence of melanoma&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;17&#44;36</span></a> such as the recent multicenter case-control study conducted by Stenehjem et al&#46;&#44; with over 1000 patients&#44; which failed to conclude that low or elevated levels of VD are associated with the incidence of melanoma&#44; although they postulate that the lower incidence of melanoma reported may possibly be in patients with VD levels between 30 ng&#47;mL and 50 ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> Lastly&#44; other studies showed that elevated levels of VD could be associated with a higher incidence of melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">20&#44;42</span></a> Particularly relevant is the study conducted by Cai et al&#46;&#44; which used a Mendelian randomization analysis&#44; with a sample size of more than 500 000 patients&#44; to eventually find a possible direct correlation between VD levels and melanoma&#46; This analysis was confirmed after performing pleiotropy tests and sensitivity analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">42</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Vitamin D and melanoma prognosis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Several studies have described that low levels of VD were associated with melanomas of worse prognosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">table 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">17&#44;25&#8211;31&#44;34&#44;37&#8211;40&#44;45&#44;46</span></a> For example&#44; a Spanish study from 2019 with 204 individuals with melanoma found that lower levels of VD were associated with tumor ulceration and a higher mitotic index&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">46</span></a> One 2020 SR and 1 MA&#44; with more than 10 000 patients&#44; studied the relationship between 25VD levels and the risk of melanoma&#8212;prognostic factors included&#8212;and concluded that patients with 25VD deficiency &#40;&#8804; 20 ng&#47;mL&#41; had a higher incidence rate&#44; as well as a higher mortality specifically associated with melanoma&#46; Similarly&#44; a direct correlation was found between BT and 25VD deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding VD supplementation&#44; a clinical trial with 114 stage II melanoma patients &#40;80&#37; of them with insufficient VD levels&#41; confirmed that VD supplementation was not associated with higher disease-free survival rates compared with non-supplementation&#46; At the 12-month follow-up&#44; patients with low 25VD levels and a BT &#8805; 3<span class="elsevierStyleHsp" style=""></span>mm had lower disease-free survival&#44; which was not the case of individuals with lower 25VD levels alone&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Vitamin D supplementation and melanoma risk</span><p id="par0050" class="elsevierStylePara elsevierViewall">Multiple studies have analyzed the incidence of melanoma in patients with VD supplementation with contradictory results&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">24&#44;25&#44;38&#44;41&#44;43</span></a> A recent cross-sectional study &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>498&#41; revealed that individuals with oral VD supplementation had a lower risk of developing melanoma &#40;0&#46;447 &#91;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#59; 95&#37;CI&#44; 0&#46;231-0&#46;862&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">43</span></a> However&#44; a clinical trial with more than 30 000 postmenopausal women&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> and a recent MA&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">23</span></a> both previously discussed&#44; did not find a decrease in melanoma rates in patients on VD supplements&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Vitamin D and response to advanced therapy</span><p id="par0055" class="elsevierStylePara elsevierViewall">In 2020&#44; Grover et al&#46; conducted a retrospective study in patients with metastatic melanoma on anti-PD-1 or anti-CTLA-4&#46; A total of 17&#37; of these patients developed immune-mediated colitis&#46; Prior VD supplementation showed a significant association with a lower risk of colitis&#46; These results were later confirmed in an independent cohort &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> A prospective study with 83 patients with metastatic melanoma on BRAF or MEK inhibitors&#44; or immunotherapy&#44; revealed that 25VD deficiency &#40;&#60; 10 ng&#47;mL&#41; was associated with a significantly lower overall and progression-free survival&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a> Recently&#44; Galus et al&#46; published the results of a clinical trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>200&#41;&#44; showing that patients with 25VD deficiency on anti-PD-1 treatment showed lower objective response rates &#40;36&#46;2&#37; vs 56&#46;0&#37;&#41;&#44; lower disease-free survival &#40;5&#46;75 months vs 11&#46;25 months&#41;&#44; and lower overall survival compared with patients with normal 25VD levels&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Vitamin D and photoprotection</span><p id="par0060" class="elsevierStylePara elsevierViewall">The relationship between the use of topical sunscreens and its impact on VD levels was also reviewed&#46; In this regard&#44; a 2019 SR concluded that regular use of topical sunscreens does not impact VD levels in healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">49</span></a> Similarly&#44; a recent study with more than 3000 patients found no association between the use of photoprotection measures&#44; including the application of topical sunscreens&#44; and decreased bone mass density or increased risk of osteoporotic fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">50</span></a> In conclusion&#44; the regular use of topical sunscreens does not impact VD levels&#44; bone mass density&#44; or increase the risk of osteoporotic fractures in healthy individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">49&#44;50</span></a></p></span></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The association between VD levels and skin cancer is as controversial as the association between VD supplementation and decreased SC&#44; or its prognosis&#46; Currently&#44; there are no established criteria or recommendations in the main guidelines on the management of SC&#44; and we lack standardized recommendations on the measurement or supplementation of VD in patients at risk or suffering from SC&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding NMSC&#44; numerous studies have reported a direct association between BCC and 25VD levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#44;11&#44;12&#44;14&#8211;17&#44;19&#8211;21</span></a> This relationship has also been reported in cutaneous squamous cell carcinoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#44;12&#44;14&#44;15&#44;17&#44;19&#8211;21</span></a> This is surprising&#44; given the growing evidence supporting VD supplementation vs other types of cancer&#44; such as colorectal or lung cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">51</span></a> This may possibly be explained by the direct relationship between 25VD levels and sun exposure&#44; a crucial risk factor for the development of NMSC&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">As for the association between melanoma and VD levels&#44; the analyzed studies differ on whether there is a direct&#44; or inverse association&#44; or no association whatsoever&#46; Although most studies report that low levels of VD or VD supplementation could reduce the risk of melanoma&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;17&#44;25&#8211;31&#44;33&#8211;35&#44;37&#8211;41&#44;43&#8211;45</span></a> we found inconclusive studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">24&#44;32&#44;36</span></a> and even some that positively correlate VD levels with the risk of melanoma or worse prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">16&#44;20&#44;42</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The role of vitamin D receptor &#40;VDR&#41; and melanoma has been studied recently&#58; some studies suggest that certain polymorphisms in the VDR gene could be associated with a higher risk of melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">52</span></a> A recent retrospective study &#40;703 melanomas&#41; stated that higher levels of VDR expression independently protected vs melanoma-related death&#44; both primary and metastatic&#46; Tumors with high rates of VDR expression showed increased anti-tumor immune activity and reduced proliferative pathways&#44; particularly Wnt-&#946;-catenin signaling&#46; In this study&#44; VD deficiency was associated with lower survival in primary melanoma&#44; especially when VDR levels were low&#46; These findings suggest a causal relationship between VD-VDR signaling and melanoma survival&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">53</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">For the relationship between VD levels or supplementation and immunotherapy in melanoma&#44; there are studies showing that low VD levels would correlate with a lower antitumor response to immunotherapy<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">48&#44;54</span></a> or even a higher rate of adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> Currently&#44; VD supplementation in melanoma patients has a grade B recommendation &#40;probably an effective recommendation&#41;&#44; with a level evidence IIb &#40;cohort studies and case-control studies&#41;&#44; although current evidence is still scarce&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a> As a matter of fact&#44; the National Comprehensive Cancer Network &#40;NCCN&#41; guidelines do not take a stance on this matter&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">55</span></a> nor does the European Society for Medical Oncology &#40;ESMO&#41; guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">56</span></a> or the 8<span class="elsevierStyleSup">th</span> edition of the American Joint Committee on Cancer &#40;AJCC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a> New studies are needed to evaluate the value of VD supplementation in melanoma patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">A recent retrospective study with 663 patients evaluated whether melanoma patients were at increased risk of developing other non-cutaneous cancers after a previous diagnosis of melanoma&#46; A total of 34 non-cutaneous tumors were found&#44; and the multivariate analysis concluded that age older than 60 years &#40;HR&#44; 3&#46;4&#59; 95&#37;CI&#44; 1&#46;5-7&#46;6&#41; and nodular subtype of melanoma &#40;HR&#44; 2&#46;2&#59; 95&#37;CI&#44; 1-4&#46;8&#41; were directly associated with the appearance of other non-cutaneous tumors&#44; but not VD levels&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limitations</span><p id="par0095" class="elsevierStylePara elsevierViewall">Our review has multiple limitations&#58; it is a narrative&#8211;not a systematic one&#8211;review&#59; many studies included are retrospective and&#47;or use several methodologies to measure variables and outcomes&#44; which complicates data comparison&#46; These factors hinder the generalization of findings and conclusions&#44; underscoring the need for properly designed prospective studies with prolonged follow-up&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">The association between VD and SC is a complex one&#46; Adequate or even elevated levels of VD could be associated with a higher risk of NMSC&#44; especially BCC&#46; As for melanoma&#44; the relationship is uncertain&#44; with contradictory results&#46; However&#44; most studies state that higher levels of VD or VD supplementation could reduce the risk of melanoma and are associated with melanomas of better prognosis&#46; Similarly&#44; elevated levels of VD or VD supplementation could be associated with a better antitumor response and fewer adverse effects with melanoma immunotherapy&#46; In conclusion&#44; to date&#44; there is still insufficient evidence to recommend VD supplementation in patients at risk of NMSC or melanoma&#46; However&#44; normal levels of VD could be associated with better therapeutic responses and prognosis in melanoma&#46; Prospective studies of high methodological quality are required to clarify the role of VD and its supplementation in SC and develop clinical guidelines accordingly&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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              "titulo" => "B&#46; Vitamin D and melanoma"
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                  "titulo" => "Vitamin D and melanoma prognosis"
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                  "titulo" => "Vitamin D supplementation and melanoma risk"
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                  "titulo" => "Vitamin D and response to advanced therapy"
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    "fechaRecibido" => "2023-12-22"
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          "palabras" => array:5 [
            0 => "Skin cancer"
            1 => "Squamous cell carcinoma"
            2 => "Melanoma"
            3 => "Vitamin D"
            4 => "Dermatology"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1843110"
          "palabras" => array:5 [
            0 => "C&#225;ncer cut&#225;neo"
            1 => "Carcinoma epidermoide"
            2 => "Melanoma"
            3 => "Vitamina D"
            4 => "Dermatolog&#237;a"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vitamin D &#40;VD&#41; deficiency has been associated with various tumors&#46; However&#44; the association between VD and skin cancer is controversial&#46; Although in non-melanoma skin cancer&#44; adequate or even high levels of VD can be associated with a higher risk of developing tumors&#44; this could be biased by the direct association between sun exposure and VD levels&#46; Regarding melanoma&#44; results are contradictory&#46; Most studies analyzed state that higher levels of VD could reduce the risk of melanoma&#44; be associated with melanomas with better prognosis and with an enhanced antitumor response&#44; and also with fewer adverse events associated with melanoma immunotherapy&#46; However&#44; prospective studies of adequate methodological quality are still needed to assess the association between VD levels and its supplementation and development&#47;prognosis in skin cancer&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La deficiencia de vitamina D &#40;VD&#41; se ha relacionado con diferentes tumores&#46; La asociaci&#243;n entre la VD y el c&#225;ncer cut&#225;neo es controvertida&#46; Para el c&#225;ncer cut&#225;neo no melanoma&#44; niveles adecuados o incluso elevados de VD podr&#237;an asociarse a un mayor riesgo tumoral&#44; aunque este hecho podr&#237;a estar sesgado por la asociaci&#243;n directa entre exposici&#243;n solar y niveles de VD&#46; En cuanto al melanoma&#44; hay resultados contradictorios&#46; La mayor&#237;a de los estudios analizados reportan que niveles m&#225;s altos de VD podr&#237;an disminuir el riesgo de melanoma&#44; podr&#237;an asociarse a melanomas con mejor pron&#243;stico y podr&#237;an correlacionarse con una mejor respuesta antitumoral y un menor perfil de efectos adversos en la inmunoterapia del melanoma&#46; Sin embargo&#44; son necesarios estudios prospectivos de adecuada calidad metodol&#243;gica que eval&#250;en la asociaci&#243;n de los niveles de VD y su suplementaci&#243;n&#44; y el desarrollo y pron&#243;stico del c&#225;ncer cut&#225;neo&#46;</p></span>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Vitamin D metabolism &#40;panel A&#41; and structure of activated vitamin D &#40;calcitriol or 1&#44;25-dihydroxycholecalciferol&#59; C27H44O3&#41; &#40;panel B&#41;&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel A&#46;</span> Vitamin D metabolism&#46; Vitamin D can be obtained through the diet&#44; or by cutaneous conversion via UVB&#44; which transforms provitamin D3 &#40;synthesized at skin level&#41; into previtamin D3&#46; The first hepatic step converts it to calcidiol or 25-hydroxyvitamin D through hepatic 25-hydroxylase&#46; The second step&#44; which occurs at renal level&#44; converts it into the active metabolite&#44; 1&#44;25-dihydroxycholecalciferol or calcitriol through renal 1-hydroxylase&#46; This mechanism is regulated&#44; among others&#44; by serum levels of calcium&#44; phosphorus&#44; and parathyroid hormone&#46; Calcitriol acts through intracellular vitamin D receptors &#40;VDR&#41;&#44; which activate the transcription and translation process of messenger RNA by synthesizing vitamin D-dependent proteins&#44; with their corresponding activity based on the target cell&#46; The excretion of vitamin D through bile is mediated by the activity of renal 24-hydroxylase&#44; which converts calcitriol into calcitroic acid&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel B</span>&#46; Structure of activated vitamin D&#46; Note that vitamin D must undergo 2 different hydroxylations to be activated&#58; activation &#35;1 &#40;green circle&#41; occurs in the liver forming 25-hydroxycholecalciferol&#44; or calcidiol&#59; activation &#35;2 &#40;red circle&#41; occurs in the kidney forming 1&#44;25-dihydroxycholecalciferol or calcitriol&#44; which is the active form&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; own elaboration and data obtained with permission from Navarro-Trivi&#241;o et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a></p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CCL&#44; chemokine &#40;C-C motif&#41; ligand&#59; CD&#44; cluster of differentiation&#59; IL&#44; interleukin&#59; NLRP-3&#44; nucleotide-binding domain&#44; leucine-rich-containing family&#44; pyrin domain-containing-3&#59; ROS&#44; reactive oxygen species&#59; Th&#44; T helper lymphocyte &#40;collaborator&#41;&#59; TLR&#44; toll-like receptor&#59; TNF&#44; tumor necrosis factor&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Fantini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">3</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Biochemical action of vitamin D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Implication at biochemical level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Possible clinical implications of vitamin D deficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of TLR2&#44; 4&#44; and 9 expression and signaling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regulation of the innate immune system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Increased frequency of autoimmune diseases- Increased severity of autoimmune diseases- Increased frequency of certain infectious processes- Early development of cardiovascular disease&#58; obesity and arteriosclerosis- Earlier and more pronounced aging &#40;accelerated dermatoporosis&#44; sarcopenia&#44; etc&#46;&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in production of TNF-&#945;&#44; IL-1&#44; IL-6&#44; and IL-23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of some cytokines that enhance the activity of T cells&#44; especially CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased production of IL-4&#44; IL-5&#44; IL-10&#44; and CCL2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased production of anti-inflammatory cytokines&#44; regulating the activity of T cells&#44; especially Th17 and enhancing Th2 activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of IL-6 production&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduced Th17 activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of IL-33 production&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduced T cell and dendritic cell activity in some autoimmune diseases&#44; such as Guillain-Barr&#233; syndrome&#44; psoriasis&#44; or rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased production of Fox P3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>regulatory T cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduced autoimmune T cell activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased lymphocyte co-stimulation via CD-28 molecule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Potential activity of cytotoxic T cells and activation of B cells under specific circumstances&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in generation of autoantibodies and ROS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fewer autoimmune cascades and inflammation control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased levels of cathelicidin LL-37 and cationic protein AMP-18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fewer infections and early and adequate control of them&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Correct activation of TLR1&#44; 2&#44; and 8 response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fewer infections and early and adequate control of them&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Controlled increase in IL-1&#946; and defensin&#44; telomere shortening reduction&#44; increase in Nrf2 levels&#44; decrease in NF-k&#946; pathway&#44; decrease in NLRP-3 levels&#44; DNA damage reduction&#44; increase in mitochondrial biogenesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regulation of cutaneous and systemic aging&#44; prevention of early and accelerated aging&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of inflammation &#40;especially T cell response&#41;&#44; decrease in RAAS activation and ROS generation&#44; and control of plasma LDL levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prevention of arteriosclerosis&#44; obesity&#44; metabolic syndrome&#44; and early cardiovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Role of vitamin D in immunosurveillance and immunosenescence&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">25&#40;OH&#41;D&#44; 25-hydroxycholecalciferol&#59; BCC&#44; basal cell carcinoma&#59; cSCC&#44; cutaneous squamous cell carcinoma&#59; MA&#44; meta-analysis&#59; MSC&#44; melanoma skin cancer&#59; NMSC&#44; non-melanoma skin cancer&#59; RCT&#44; randomized clinical trial&#59; SC&#44; skin cancer&#59; SCC&#44; squamous cell carcinoma&#59; SR&#44; systematic review&#59; VD&#44; vitamin D &#40;no subtype specification&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Authors and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type&#44; methodology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van Dam et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">10</span></a> 2000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective&#44; multicenter cohorts- 8-year follow-up of patients with different dietary habits to evaluate the risk of breast cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Males between the ages of 40 and 75 years without a previous history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No significant correlation was found between the use or levels of 25VD and the appearance of BCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asgari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a> 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">440&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Retrospective&#44; single-center case-control study- Comparison of vitamin D levels between patients with BCC and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- All patients listed for BCC surgery-Healthy controls without dermatological diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- 25VD levels were significantly slightly higher in the BCC patient group vs the control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">12</span></a> 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective multicenter cohorts- 5-year follow-up of patients to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caucasian males &#8805; 65 years old of with or without prior history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25VD levels showed an inverse correlation with the history of SC and the risk of developing SC&#46; No correlation was found between VD intake and the history or occurrence of SC&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Phase III RCT &#40;<span class="elsevierStyleInterRef" id="intr0005" href="ctgov:NCT00000611">NCT00000611</span>&#41;&#46;- Development of SC in patients with supplementation of 1 g calcium and 400 IU of VD&#47;day vs placebo in a 7-year follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postmenopausal women with or without a previous history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The rates of SC occurrence in patients with supplementation did not differ from the control group&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eide et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">14</span></a> 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3223&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Retrospective&#44; single-center&#44; cohort study- 8-year follow-up to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caucasian patients who underwent blood tests from 1997 through 2001 in the study of possible osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with non-insufficient 25VD levels &#40;&#62;15 ng&#47;mL&#41; had a significantly higher rate of NMSC&#44; especially in photo-exposed areas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">15</span></a> 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4641&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective multicentric cohort study- 18-year follow-up of patients to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nurses from the British NHS undergoing blood test from 1989 through 1990&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A positive and statistically significant correlation was found between 25VD levels and SC onset&#44; both MSC and NMSC&#46;Patients in the highest quartile &#40;highest 25VD levels&#41; had the highest risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van der Pols et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">16</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective multicentric cohort study- 8-year follow-up of patients to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Healthy patients of any age and background who voluntarily participated in a SC prevention study from 1992 through 1996&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25VD levels &#62;<span class="elsevierStyleHsp" style=""></span>75 ng&#47;mL were associated with an increased risk of BCC&#44; while levels &#60; 75 ng&#47;mL were associated with increased risk of cSCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">17</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2317&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR and MA- Cohorts&#44; case-control&#44; and cross-sectional studies with &#62;<span class="elsevierStyleHsp" style=""></span>10 patients were included&#44; which assessed the occurrence of SC based on 25VD levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset in relation to 25VD levels until January 2013 &#40;20 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated 25VD levels were associated with a higher risk of NMSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van Deventer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">18</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Cross sectional&#44; single-center- Measurement of 25VD levels in patients diagnosed with MSC or NMSC in a tertiary referral center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with MSC or NMSC during the summer of 2015 in a tertiary referral center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No association was ever found between 25VD levels and the occurrence of NMSC&#44; or between 25VD levels and previous history of NMSC&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soares et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">241&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective&#44; single-center cases and control- Measurement of 25VD levels in patients diagnosed with BCC or cSCC in a tertiary referral center&#44; comparing them with healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A random group of NMSC-diagnosed patients from September 2016 through September 2017 regardless of age or history&#44; matched with healthy controls in a NMSC 5&#58;1 control ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Most of the sample &#40;both controls and NMSC patients&#41; had low or insufficient levels of 25VD- 25VD levels were significantly higher in patients with NMSC vs the control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vojdeman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">212 244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Retrospective&#44; multicentric&#44; cohort study- Measurement of 25VD levels in a national population cohort and analysis of the incidence of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients collected in the Danish national registry who had documented 25VD levels from 2004 through 2010&#46; Incidence of SC was analyzed until 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated levels of 25VD were associated with a higher and statistically significant incidence of NMSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morgado-&#193;guila et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">6</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective&#44; single-center cases and controls- Measurement of 25VD levels in patients diagnosed with BCC or cSCC&#44; comparing them with healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subjects diagnosed with cSCC or BCC in a tertiary referral center from 2015 through 2019 vs controls attending the clinic for a different reason &#40;unrelated to SC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It was significantly found that lower levels of 25VD were associated with a significantly lower incidence of NMSC&#46; Patients with values &#62;<span class="elsevierStyleHsp" style=""></span>18 ng&#47;mL had an up to 7 times higher risk of NMSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 067&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR and MA- All cohort&#44; clinical&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; clinical&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset until September 2020 &#40;24 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A direct association was found between 25VD levels and the risk of NMSC&#44; as well as between 25VD intake and the risk of NMSC&#46; This risk seemed more evident in observational than in clinical trials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abdelwahab et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">22</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>200 000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR- All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset until January 2022 &#40;10 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It could not be concluded that normal&#44; elevated&#44; or low levels of 25VD are associated with a higher or lower risk of NMSC&#46; Great heterogeneity observed in the results of the included studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Main studies on the association of vitamin D and non-melanoma skin cancer&#46;</p>"
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      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">25VD&#44; 25-hydroxycholecalciferol&#59; BT&#44; Breslow thickness&#59; DFS&#44; disease-free survival&#59; GWAS&#44; Genome Wide Association Studies&#59; MA&#44; meta-analysis&#59; MSC&#44; melanoma skin cancer&#59; NMSC&#44; non-melanoma skin cancer&#59; RCT&#44; randomized clinical trial&#59; SC&#44; skin cancer&#59; SR&#44; systematic review&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Authors and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type&#44; methodology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asgari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a> 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 611&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter retrospective cohort study-Patients followed in a study of supplementation with 25VD that analyzed the incidence of melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Participation in the Vitamins and Lifestyle cohort study analyzing tumor incidence in patients with various dietary supplements&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The supplementary intake of 25VD and its association with a lower incidence of melanoma was inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Newton-Bishop et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">25</span></a> 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">271&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective single-center case-control study-Patients diagnosed with melanoma in a tertiary referral center vs a control cohort of healthy patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma in a tertiary referral center from 2000 through 2005 were compared&#44; regardless of their background&#46;Patients were compared with a healthy control cohort from a melanoma registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-There was no significant reduction in the risk of melanoma in patients on 25VD supplements&#46;-Significantly higher levels of 25VD were associated with a lower risk of melanoma and a lower BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Phase III RCT &#40;<span class="elsevierStyleInterRef" id="intr0010" href="ctgov:NCT00000611">NCT00000611</span>&#41;-Development of SC in patients supplemented with 1g calcium and 400 IU of VD&#47;day vs placebo in a 7-year follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postmenopausal women with or without a history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The rates of melanoma in patients on supplements did not differ from the control group without supplements&#46; However&#44; supplemented patients with a history of NMSC showed a significantly lower risk of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van der Pols et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">16</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective multicenter cohort study- 8-year follow-up of patients to evaluate the occurrence of SC&#44; measuring the levels of 25VD before follow-up&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Healthy patients of any age and background who voluntarily participated in a SC prevention study from 1992 through 1996&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Levels of 25VD &#62;<span class="elsevierStyleHsp" style=""></span>75 ng&#47;mL were associated with a higher risk of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gambichler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">26</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">764&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center&#44; cross-sectional study-Measurement of 25VD levels in patients at the time of melanoma diagnosis in a tertiary referral center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with melanoma from 2009 through 2012&#44; comparing 25&#40;OH&#41;D levels and histological parameters and stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It was found that lower levels of 25VD &#40;&#8804; 30 ng&#47;mL&#41; were associated with a higher BT and a higher tumor stage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">17</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1420&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-SR and MA-Included cohort and case-control&#44; cross-sectional study with &#62;<span class="elsevierStyleHsp" style=""></span>10 patients that evaluated the occurrence of SC based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients evaluating SC occurrence until January 2013 &#40;20 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No significant results associating 25VD levels and melanoma were found&#46; However&#44; a significant inverse relationship was found between BT and the levels of 25VD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bade et al&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">45</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center&#44; case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma in a tertiary referral center with levels of 25VD on record&#44; vs a healthy control group from 2010 through 2013&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deficiency &#40;&#8804; 20 ng&#47;mL&#41; of 25VD was more frequent in patients with melanoma vs controls&#46;- Lower levels of 25VD were associated with a higher BT and a lower specific melanoma survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Newton-Bishop et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">27</span></a> 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2182&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center&#44; cross-sectional&#44; prospective study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2001 through 2003&#46; Patients with positive lymph nodes and unknown primary were excluded&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower levels of 25VD are associated with melanoma of worse prognosis &#40;especially more ulcerated&#41; and higher specific mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wyatt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">28</span></a> 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Cross-sectional&#44; single-center study-Measurement of 25VD levels in patients at the time of melanoma diagnosis&#44; followed by successive measurements at the follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with MSC from July 2010 through July 2011&#44; with comparisons between the levels of 25VD and the histological parameters of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Levels &#8804; 50 ng&#47;mL of 25VD were associated with an almost 4 times higher BT&#44; but not with a higher number of mitoses&#46;- Patients with levels of 25VD &#8805; 70 ng&#47;mL did not have lower incidence rates of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Saiag et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">29</span></a> 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center&#44; cohort study-Measurement of 25VD levels in patients at the time of melanoma diagnosis&#44; followed by successive measurements at the follow-up&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with melanoma from 2003 through 2008 who agreed to initial and serial measurement of 25VD levels&#46; Follow-up was conducted until 2013&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Lower levels of 25VD were found in patients with higher BT&#44; ulceration&#44; or staging&#46;- The increase rate in these values did not improve specific melanoma prognosis or the overall survival for that matter&#44; suggesting that the initial value of 25VD levels may be biased by undetected or unanalyzed confounding factors&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Timerman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">30</span></a> 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center&#44; cohort study-Measurement of 25VD levels in patients diagnosed with melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with MSC diagnosed from 2007 through 2013 who had their 25VD levels measured up to 1 year before or 1 year after diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Deficiency &#40;&#8804; 20 ng&#47;mL&#41; of 25VD was associated with a higher stage&#44; ulceration&#44; and mitotic index of melanoma&#46;- In patients with stage IV&#44; this deficiency was associated with worse specific melanoma prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">31</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center&#44; cross-sectional study-Measurement of 25VD levels in a cohort of patients diagnosed with melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2001 through 2013&#44; with measurements of 25VD levels up to 6 months after diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Direct association between low levels of 25VD and a higher BT&#44; more ulceration&#44; the desmoplastic subtype&#44; and the mitotic index&#46;- No relationship was ever found between 25VD levels and melanoma metastasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipplaa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">32</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">341&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter&#44; cross-sectional study-Measurement of 25VD levels in a cohort of patients diagnosed with melanoma stage IIB-IIIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma IIB-IIIC who were in a RCT with bevacizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- No relationship was ever found between 25VD levels and BT&#44; specific melanoma survival&#44; or overall survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vojdeman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">212 244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter&#44; retrospective&#44; cohort study-Measurement of 25VD levels in a national population cohort and analysis of the SC incidence rate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients were collected from the Danish national registry with documented 25VD levels from 2004 through 2010&#44; and the SC incidence rate was analyzed until 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated levels of 25VD were associated with a statistically significant and higher incidence of MSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cattaruza et al&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">33</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">236&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Ambispective&#44; single-center&#44; case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma with their 25VD levels on record vs a healthy control group collected subsequently&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A statistically significant association was found between insufficient &#40;20&#46;01-30 ng&#47;mL&#41; and deficient &#40;&#8804; 20 ng&#47;mL&#41; 25VD levels and the development of MSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tsai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 166&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR and MA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies with &#62;<span class="elsevierStyleHsp" style=""></span>20 patients until November 2018 evaluating the relationship between melanoma and 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Patients with deficiency &#40;&#8804; 20 ng&#47;mL&#41; of 25VD had a higher incidence rate of melanoma&#46;- Positive correlation between BT and 25VD deficiency&#46;- Patients with 25VD deficiency had higher mortality rates from melanoma than patients with melanoma and levels &#62;<span class="elsevierStyleHsp" style=""></span>20 ng&#47;mL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Befon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">35</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">198&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center case-control study-Measurement of 25VD levels in a cohort of patients with melanoma vs a healthy cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2011 through 2014 with 25VD levels on record and comparison between them and a control group from the same period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Patients with melanoma had lower mean levels of 25VD vs the control group &#40;25 vs 21 ng&#47;mL&#44; respectively&#41;&#46; - No association was ever found between 25VD levels and BT&#44; ulceration&#44; stage&#44; or type of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stenehjem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1416&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; multicenter&#44; case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma in a national Norwegian cohort&#46; They were matched with healthy controls from a different national cohort in the same country&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- It could not be statistically demonstrated that elevated or reduced levels of 25VD are associated with a higher or lower risk of melanoma&#44; although data suggest that probably the lower risk group is the one with levels between 30 ng&#47;mL and 50 ng&#47;mL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lombardo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">279&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2016 through 2019 vs healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Melanoma growth was more frequent in patients with 25VD deficiency &#40;&#8804; 30 ng&#47;mL&#41;&#46;- No significant association was ever found between 25VD levels and BT&#46; However&#44; lower levels of 25VD were reportedly associated with a higher mitotic index and a BT cutoff point &#62;<span class="elsevierStyleHsp" style=""></span>1 mm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johansson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center RCT-Analysis of DFS in patients with stage II melanoma vs placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with stage II melanoma diagnosed from 2011 through 2015&#46; Supplementation with 25VD was compared to non-supplementation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- 25VD supplementation was not associated with better DFS rates vs non-supplementation&#46;- The combination of low levels of 25VD and BT &#8805; 3 mm reported lower rates of DFS which was not so for lower levels of 25VD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">39</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">286&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center cohort study-Analysis of the incidence rate and characteristics of melanoma in a 25VD level-based cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma&#44; in whom 25VD levels were measured from 2011 through 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The combination of 25VD levels<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BT <span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>3 was associated with less DFS unlike lower levels of 25VD &#60;<span class="elsevierStyleHsp" style=""></span>9&#46;25 ng&#47;mL&#44; which were associated with more ulceration and lower overall survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gracia-Darder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center cohort study-Analysis of the melanoma incidence rate and its characteristics in a 25VD level-based cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma&#44; in whom 25VD levels were measured from 1998 through 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low levels of 25VD were associated with a higher BT&#44; lower specific melanoma survival&#44; and lower overall survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sha et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">41</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">411 436&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter&#44; cross-sectional study-Analysis of the association between VD supplementation and a lower melanoma risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients aged between 40 and 69 included in the English national registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Up to 21&#37; of the population had VD deficiency &#40;&#8804; 20&#41; and 34&#37; VD insufficiency &#40;&#8804; 30&#41;-Multivitamin supplementation was found to potentially reduce the risk of melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">42</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>500 000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Mendelian randomization analysis-Analysis of causal relationship between 25VD levels and melanoma&#44; with subsequent pleiotropy and sensitivity analysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It included studies from the literature up to 2023 with which a GWAS could be conducted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive association between 25VD levels and melanoma&#44; even after conducting pleiotropy testing and sensitivity analysis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kanasuo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">43</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">498&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center&#44; cohort study-Healthy patients attending either oncological or non-oncological dermatological visits&#44; with their 25VD levels on record&#44; and in a subgroup&#44; with oral VD supplementation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients attending dermatological visits aged between 18 and 80 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- No association was ever found between 25VD levels and the risk of melanoma&#46;- However&#44; 25VD supplementation was indeed associated with a lower risk of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shellenberger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-SR and MA-14 case-control and prospective cohort studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All prospective cohort and case-control studies with &#62;<span class="elsevierStyleHsp" style=""></span>20 patients up until July 2022 were included&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher incidence rate of melanoma with 25VD deficiency &#40;&#8804; 30 ng&#47;mL&#41; and a higher BT with lower 25VD levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Main studies on the association of vitamin D and melanoma&#46;</p>"
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      ]
      4 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AE&#44; adverse events&#59; BRAF&#44; B-rapidly accelerated fibrosarcoma&#59; CTLA-4&#44; cytotoxic T-lymphocyte-associated protein 4&#59; MEK&#44; mitogen-activated protein kinase&#59; PD&#44; programmed cell death protein&#59; 25VD&#44; 25-hydroxycholecalciferol&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Authors and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study&#44; morphology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grover et al&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">213&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center cohort study&#46;-Comparison of the colitis incidence rate in melanoma patients on immunotherapy based on supplementation or not with 25VD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with unresectable or metastatic melanoma on anti PD-1 or anti CTLA-4&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Supplementation with 25VD reduced the risk of immune-mediated colitis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reichrath et al&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center cohort study-Comparison of response to immunotherapy and targeted therapy in melanoma based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with unresectable or metastatic melanoma on BRAF&#47;MEK inhibitors or immunotherapy with anti-PD1&#46; Analysis of response and AE based on 25VD levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-25VD severe deficiency<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> was associated with a lower overall survival and progression-free survival&#44; and a higher tumor burden&#46;-Major AE in patients with 25VD levels &#8805; 10 ng&#47;mL and mutated BRAF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Galus et al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">54</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2023 200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Non-randomized&#44; single center clinical trial-Comparison of immunotherapy response in melanoma based on vitamin D levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with unresectable melanoma on first-line therapy with anti PD1 &#40;nivolumab or pembrolizumab&#41;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with VD deficiency had a lower response rate&#44; lower progression-free survival&#44; and a lower overall survival vs those with normal levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">25VD severe deficiency was defined as levels &#60;<span class="elsevierStyleHsp" style=""></span>10 ng&#47;mL&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Main studies on vitamin D and response to advanced therapy in melanoma&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:58 [
            0 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D and the skin&#58; An update for dermatologists"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; Kechichian"
                            1 => "K&#46; Ezzedine"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40257-017-0323-8"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Clin Dermatol&#46;"
                        "fecha" => "2018"
                        "volumen" => "19"
                        "paginaInicial" => "223"
                        "paginaFinal" => "235"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28994020"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0007091220308540"
                          "estado" => "S300"
                          "issn" => "00070912"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of vitamin D in reducing cancer risk and progression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Feldman"
                            1 => "A&#46;V&#46; Krishnan"
                            2 => "S&#46; Swami"
                            3 => "E&#46; Giovannucci"
                            4 => "B&#46;J&#46; Feldman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrc3691"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Cancer&#46;"
                        "fecha" => "2014"
                        "volumen" => "14"
                        "paginaInicial" => "342"
                        "paginaFinal" => "357"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24705652"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D as a shield against aging"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46; Fantini"
                            1 => "C&#46; Corinaldesi"
                            2 => "A&#46; Lenzi"
                            3 => "S&#46; Migliaccio"
                            4 => "C&#46; Crescioli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/ijms24054546"
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Mol Sci&#46;"
                        "fecha" => "2023"
                        "volumen" => "24"
                        "paginaInicial" => "4546"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36901976"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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Controversies in Dermatology
Vitamin D and Skin Cancer: A Controversial Society. Literature Update and Review
Vitamina D y cáncer cutáneo: una asociación controvertida. Actualización y revisión de la literatura
M. Mansilla-Poloa,b, M. Luque-Lunac, D. Morgado-Carrascoc,d,
Corresponding author
morgadodaniel8@gmail.com

Corresponding author.
a Servicio de Dermatología, Hospital Universitario y Politécnico La Fe, Valencia, Spain
b Instituto de Investigación Sanitaria (IIS) La Fe, Valencia, Spain
c Servicio de Dermatología, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
d Servicio de Dermatología, Hospital de Figueres, Fundació Salut Empordà, Figueres, Girona, Spain
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        "titulo" => "Vitamina D y c&#225;ncer cut&#225;neo&#58; una asociaci&#243;n controvertida&#46; Actualizaci&#243;n y revisi&#243;n de la literatura"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Vitamin D metabolism &#40;panel A&#41; and structure of activated vitamin D &#40;calcitriol or 1&#44;25-dihydroxycholecalciferol&#59; C27H44O3&#41; &#40;panel B&#41;&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel A&#46;</span> Vitamin D metabolism&#46; Vitamin D can be obtained through the diet&#44; or by cutaneous conversion via UVB&#44; which transforms provitamin D3 &#40;synthesized at skin level&#41; into previtamin D3&#46; The first hepatic step converts it to calcidiol or 25-hydroxyvitamin D through hepatic 25-hydroxylase&#46; The second step&#44; which occurs at renal level&#44; converts it into the active metabolite&#44; 1&#44;25-dihydroxycholecalciferol or calcitriol through renal 1-hydroxylase&#46; This mechanism is regulated&#44; among others&#44; by serum levels of calcium&#44; phosphorus&#44; and parathyroid hormone&#46; Calcitriol acts through intracellular vitamin D receptors &#40;VDR&#41;&#44; which activate the transcription and translation process of messenger RNA by synthesizing vitamin D-dependent proteins&#44; with their corresponding activity based on the target cell&#46; The excretion of vitamin D through bile is mediated by the activity of renal 24-hydroxylase&#44; which converts calcitriol into calcitroic acid&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel B</span>&#46; Structure of activated vitamin D&#46; Note that vitamin D must undergo 2 different hydroxylations to be activated&#58; activation &#35;1 &#40;green circle&#41; occurs in the liver forming 25-hydroxycholecalciferol&#44; or calcidiol&#59; activation &#35;2 &#40;red circle&#41; occurs in the kidney forming 1&#44;25-dihydroxycholecalciferol or calcitriol&#44; which is the active form&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; own elaboration and data obtained with permission from Navarro-Trivi&#241;o et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a></p>"
        ]
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Vitamin D &#40;VD&#41; is a prohormone obtained mainly from exposure to ultraviolet B &#40;UVB&#41; radiation and diet &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> VD plays an essential role in bone health and immunity&#46; Furthermore&#44; VD has an antineoplastic effect by regulating cell proliferation&#44; differentiation&#44; migration&#44; and apoptosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">2&#44;3</span></a> VD has been associated with a lower risk of colorectal&#44; breast&#44; and prostate cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">4</span></a> However&#44; this association is controversial in the case of skin cancer &#40;SC&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#44;6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Since 2009&#44; 25-hydroxyvitamin D or colecalciferol &#40;25VD&#41; has been quantified to recognize VD levels&#46; According to the National Academy of Medicine &#40;NAM&#41;&#44; 25VD levels &#62;<span class="elsevierStyleHsp" style=""></span>20 ng&#47;mL are sufficient for optimal health&#44; while the American Endocrine Society &#40;AES&#41; suggests levels &#62;<span class="elsevierStyleHsp" style=""></span>30 ng&#47;mL&#59; insufficient levels range between 20 ng&#47;mL and 30 ng&#47;mL&#44; and deficient levels are those &#60;<span class="elsevierStyleHsp" style=""></span>20 ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a> In recent years&#44; VD deficiency and insufficiency have been regarded as having &#8220;pandemic proportions&#46;&#8221; Up to 70&#37; of the European population may have insufficient levels&#44; even in countries with high sun exposure&#44; such as Mediterranean regions&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">7</span></a> Some authors attribute this phenomenon to reduced sunlight exposure and&#47;or diets low in VD-rich foods&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a> However&#44; other authors consider the cutoff of 20 ng&#47;mL or 30 ng&#47;mL too high&#44; which would explain why most of the European population has low VD levels without accompanying symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">8</span></a> Recently&#44; considering the contradictory evidence on the utility of measuring and supplementing VD&#44; the U&#46;S&#46; Preventive Services Task Force has ill-advised measuring and supplementing VD levels in healthy individuals&#44; something that should only be done in patients at risk of osteoporosis or fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">As previously noted&#44; the relationship between VD and SC is controversial&#44; and the evidence is often contradictory&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#44;6</span></a> In this article&#44; we will be reviewing the association between VD and the development and prognosis of SC&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We conducted a narrative review of currently available literature&#46; Searches were conducted in Spanish and English across Medline and Google Scholar from September through October 2023 using the terms &#8220;vitamin D&#44;&#8221; &#8220;calcitriol&#44;&#8221; &#8220;colecalciferol&#44;&#8221; &#8220;skin cancer&#44;&#8221; &#8220;melanoma&#44;&#8221; &#8220;squamous cell carcinoma&#44;&#8221; &#8220;basal cell carcinoma&#44;&#8221; &#8220;immunotherapy&#44;&#8221; &#8220;supplementation&#44;&#8221; &#8220;response to targeted therapy&#44;&#8221; and &#8220;response to immunotherapy&#46;&#8221; The search included articles from January 1<span class="elsevierStyleSup">st</span>&#44; 2000 through September 1<span class="elsevierStyleSup">st</span>&#44; 2023&#46; Prospective and retrospective studies with &#8805; 10 patients&#44; and systematic reviews &#40;SRs&#41; and meta-analyses &#40;MAs&#41;&#44; were included&#46; Articles were screened based on their abstracts and selected based on their relevance&#46; Two authors &#40;MMP and DMC&#41; conducted the search and selected the articles&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">A&#46; Vitamin D and non-melanoma skin cancer</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Development of non-melanoma skin cancer</span><p id="par0025" class="elsevierStylePara elsevierViewall">Multiple studies have tried to elucidate the relationship between 25VD levels or VD supplementation and non-melanoma skin cancer &#40;NMSC&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">table 2</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#44;10&#8211;22</span></a> Most found that sufficient VD levels &#40;&#8805; 20 ng&#47;mL or &#8805; 30 ng&#47;mL depending on the studies&#41; were associated with a higher risk of NMSC&#44; especially basal cell carcinoma &#40;BCC&#41;&#46; Nonetheless&#44; two recent SRs have provided contradictory results&#46; Back in 2021&#44; Caini et al&#46; published 1 SR and 1 MA that included 24 studies&#58; 3 prospective and 21 retrospective &#40;58 067 patients overall&#41;&#46; They found a direct association between 25VD levels and the risk of NMSC&#44; and between a higher 25VD intake and the risk of NMSC&#46; This risk seemed more evident in observational studies than in clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a> However&#44; in 2022&#44; in a different SR that included 10 studies and 204 000 patients&#44; Abdelwahab et al&#46; stated that it could not be concluded that there was an actual relationship between 25VD levels and the occurrence of BCC&#46; They also said that this inconsistency was due to the lack of homogeneity of the included studies&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">22</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Effects of vitamin D supplementation on skin cancer</span><p id="par0030" class="elsevierStylePara elsevierViewall">A randomized placebo-controlled trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36 282&#41; evaluated the effects of supplementation with 400 IU of VD and 1000<span class="elsevierStyleHsp" style=""></span>mg of calcium on the risk of developing NMSC and melanoma in postmenopausal women&#46; The mean follow-up was 7 years&#46; Supplementation failed to reduce the overall incidence of NMSC or melanoma&#46; In a subanalysis&#44; the group of women with a history of NMSC who received supplementation had a lower risk of developing melanoma &#40;hazard ratio&#44; 0&#46;43&#59; 95&#37;CI&#44; 0&#46;21-0&#46;90&#41; compared with the placebo group&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> One MA from 2020 that included prospective studies only &#40;13 studies with&#44; overall&#44; more than 200 000 patients&#41; also failed to reveal a higher risk of cutaneous squamous cell carcinoma or melanoma but did show a higher risk of basal cell carcinomas in individuals who were on VD supplements&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">23</span></a> Similar results were observed in the SR conducted by Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">B&#46; Vitamin D and melanoma</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Development of melanoma</span><p id="par0035" class="elsevierStylePara elsevierViewall">Numerous studies have associated VD with the development or progression of melanoma &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">table 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;16&#44;17&#44;20&#44;24&#8211;44</span></a> Certain reports link lower levels of VD with a higher incidence of melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">33&#8211;35&#44;37&#44;44&#44;45</span></a> One 2023 SR and 1 MA&#44; which collected 14 case-control studies and prospective cohorts for a total of 6111 patients confirmed a higher incidence of melanoma and a higher Breslow thickness &#40;BT&#41; in patients with VD insufficiency &#40;&#8804; 30 ng&#47;mL&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a> However&#44; other studies have not found a relationship between VD levels and the incidence of melanoma&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;17&#44;36</span></a> such as the recent multicenter case-control study conducted by Stenehjem et al&#46;&#44; with over 1000 patients&#44; which failed to conclude that low or elevated levels of VD are associated with the incidence of melanoma&#44; although they postulate that the lower incidence of melanoma reported may possibly be in patients with VD levels between 30 ng&#47;mL and 50 ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> Lastly&#44; other studies showed that elevated levels of VD could be associated with a higher incidence of melanoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">20&#44;42</span></a> Particularly relevant is the study conducted by Cai et al&#46;&#44; which used a Mendelian randomization analysis&#44; with a sample size of more than 500 000 patients&#44; to eventually find a possible direct correlation between VD levels and melanoma&#46; This analysis was confirmed after performing pleiotropy tests and sensitivity analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">42</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Vitamin D and melanoma prognosis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Several studies have described that low levels of VD were associated with melanomas of worse prognosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">table 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">17&#44;25&#8211;31&#44;34&#44;37&#8211;40&#44;45&#44;46</span></a> For example&#44; a Spanish study from 2019 with 204 individuals with melanoma found that lower levels of VD were associated with tumor ulceration and a higher mitotic index&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">46</span></a> One 2020 SR and 1 MA&#44; with more than 10 000 patients&#44; studied the relationship between 25VD levels and the risk of melanoma&#8212;prognostic factors included&#8212;and concluded that patients with 25VD deficiency &#40;&#8804; 20 ng&#47;mL&#41; had a higher incidence rate&#44; as well as a higher mortality specifically associated with melanoma&#46; Similarly&#44; a direct correlation was found between BT and 25VD deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding VD supplementation&#44; a clinical trial with 114 stage II melanoma patients &#40;80&#37; of them with insufficient VD levels&#41; confirmed that VD supplementation was not associated with higher disease-free survival rates compared with non-supplementation&#46; At the 12-month follow-up&#44; patients with low 25VD levels and a BT &#8805; 3<span class="elsevierStyleHsp" style=""></span>mm had lower disease-free survival&#44; which was not the case of individuals with lower 25VD levels alone&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Vitamin D supplementation and melanoma risk</span><p id="par0050" class="elsevierStylePara elsevierViewall">Multiple studies have analyzed the incidence of melanoma in patients with VD supplementation with contradictory results&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">24&#44;25&#44;38&#44;41&#44;43</span></a> A recent cross-sectional study &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>498&#41; revealed that individuals with oral VD supplementation had a lower risk of developing melanoma &#40;0&#46;447 &#91;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;016&#59; 95&#37;CI&#44; 0&#46;231-0&#46;862&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">43</span></a> However&#44; a clinical trial with more than 30 000 postmenopausal women&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> and a recent MA&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">23</span></a> both previously discussed&#44; did not find a decrease in melanoma rates in patients on VD supplements&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Vitamin D and response to advanced therapy</span><p id="par0055" class="elsevierStylePara elsevierViewall">In 2020&#44; Grover et al&#46; conducted a retrospective study in patients with metastatic melanoma on anti-PD-1 or anti-CTLA-4&#46; A total of 17&#37; of these patients developed immune-mediated colitis&#46; Prior VD supplementation showed a significant association with a lower risk of colitis&#46; These results were later confirmed in an independent cohort &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">table 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> A prospective study with 83 patients with metastatic melanoma on BRAF or MEK inhibitors&#44; or immunotherapy&#44; revealed that 25VD deficiency &#40;&#60; 10 ng&#47;mL&#41; was associated with a significantly lower overall and progression-free survival&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a> Recently&#44; Galus et al&#46; published the results of a clinical trial &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>200&#41;&#44; showing that patients with 25VD deficiency on anti-PD-1 treatment showed lower objective response rates &#40;36&#46;2&#37; vs 56&#46;0&#37;&#41;&#44; lower disease-free survival &#40;5&#46;75 months vs 11&#46;25 months&#41;&#44; and lower overall survival compared with patients with normal 25VD levels&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Vitamin D and photoprotection</span><p id="par0060" class="elsevierStylePara elsevierViewall">The relationship between the use of topical sunscreens and its impact on VD levels was also reviewed&#46; In this regard&#44; a 2019 SR concluded that regular use of topical sunscreens does not impact VD levels in healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">49</span></a> Similarly&#44; a recent study with more than 3000 patients found no association between the use of photoprotection measures&#44; including the application of topical sunscreens&#44; and decreased bone mass density or increased risk of osteoporotic fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">50</span></a> In conclusion&#44; the regular use of topical sunscreens does not impact VD levels&#44; bone mass density&#44; or increase the risk of osteoporotic fractures in healthy individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">49&#44;50</span></a></p></span></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">The association between VD levels and skin cancer is as controversial as the association between VD supplementation and decreased SC&#44; or its prognosis&#46; Currently&#44; there are no established criteria or recommendations in the main guidelines on the management of SC&#44; and we lack standardized recommendations on the measurement or supplementation of VD in patients at risk or suffering from SC&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding NMSC&#44; numerous studies have reported a direct association between BCC and 25VD levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#44;11&#44;12&#44;14&#8211;17&#44;19&#8211;21</span></a> This relationship has also been reported in cutaneous squamous cell carcinoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">6&#44;12&#44;14&#44;15&#44;17&#44;19&#8211;21</span></a> This is surprising&#44; given the growing evidence supporting VD supplementation vs other types of cancer&#44; such as colorectal or lung cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">51</span></a> This may possibly be explained by the direct relationship between 25VD levels and sun exposure&#44; a crucial risk factor for the development of NMSC&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">As for the association between melanoma and VD levels&#44; the analyzed studies differ on whether there is a direct&#44; or inverse association&#44; or no association whatsoever&#46; Although most studies report that low levels of VD or VD supplementation could reduce the risk of melanoma&#44;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;17&#44;25&#8211;31&#44;33&#8211;35&#44;37&#8211;41&#44;43&#8211;45</span></a> we found inconclusive studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">24&#44;32&#44;36</span></a> and even some that positively correlate VD levels with the risk of melanoma or worse prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">16&#44;20&#44;42</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The role of vitamin D receptor &#40;VDR&#41; and melanoma has been studied recently&#58; some studies suggest that certain polymorphisms in the VDR gene could be associated with a higher risk of melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">52</span></a> A recent retrospective study &#40;703 melanomas&#41; stated that higher levels of VDR expression independently protected vs melanoma-related death&#44; both primary and metastatic&#46; Tumors with high rates of VDR expression showed increased anti-tumor immune activity and reduced proliferative pathways&#44; particularly Wnt-&#946;-catenin signaling&#46; In this study&#44; VD deficiency was associated with lower survival in primary melanoma&#44; especially when VDR levels were low&#46; These findings suggest a causal relationship between VD-VDR signaling and melanoma survival&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">53</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">For the relationship between VD levels or supplementation and immunotherapy in melanoma&#44; there are studies showing that low VD levels would correlate with a lower antitumor response to immunotherapy<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">48&#44;54</span></a> or even a higher rate of adverse effects&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> Currently&#44; VD supplementation in melanoma patients has a grade B recommendation &#40;probably an effective recommendation&#41;&#44; with a level evidence IIb &#40;cohort studies and case-control studies&#41;&#44; although current evidence is still scarce&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a> As a matter of fact&#44; the National Comprehensive Cancer Network &#40;NCCN&#41; guidelines do not take a stance on this matter&#44;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">55</span></a> nor does the European Society for Medical Oncology &#40;ESMO&#41; guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">56</span></a> or the 8<span class="elsevierStyleSup">th</span> edition of the American Joint Committee on Cancer &#40;AJCC&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a> New studies are needed to evaluate the value of VD supplementation in melanoma patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">A recent retrospective study with 663 patients evaluated whether melanoma patients were at increased risk of developing other non-cutaneous cancers after a previous diagnosis of melanoma&#46; A total of 34 non-cutaneous tumors were found&#44; and the multivariate analysis concluded that age older than 60 years &#40;HR&#44; 3&#46;4&#59; 95&#37;CI&#44; 1&#46;5-7&#46;6&#41; and nodular subtype of melanoma &#40;HR&#44; 2&#46;2&#59; 95&#37;CI&#44; 1-4&#46;8&#41; were directly associated with the appearance of other non-cutaneous tumors&#44; but not VD levels&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limitations</span><p id="par0095" class="elsevierStylePara elsevierViewall">Our review has multiple limitations&#58; it is a narrative&#8211;not a systematic one&#8211;review&#59; many studies included are retrospective and&#47;or use several methodologies to measure variables and outcomes&#44; which complicates data comparison&#46; These factors hinder the generalization of findings and conclusions&#44; underscoring the need for properly designed prospective studies with prolonged follow-up&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">The association between VD and SC is a complex one&#46; Adequate or even elevated levels of VD could be associated with a higher risk of NMSC&#44; especially BCC&#46; As for melanoma&#44; the relationship is uncertain&#44; with contradictory results&#46; However&#44; most studies state that higher levels of VD or VD supplementation could reduce the risk of melanoma and are associated with melanomas of better prognosis&#46; Similarly&#44; elevated levels of VD or VD supplementation could be associated with a better antitumor response and fewer adverse effects with melanoma immunotherapy&#46; In conclusion&#44; to date&#44; there is still insufficient evidence to recommend VD supplementation in patients at risk of NMSC or melanoma&#46; However&#44; normal levels of VD could be associated with better therapeutic responses and prognosis in melanoma&#46; Prospective studies of high methodological quality are required to clarify the role of VD and its supplementation in SC and develop clinical guidelines accordingly&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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          "identificador" => "xres2190115"
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          "titulo" => "Introduction"
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          "titulo" => "Materials and methods"
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          "titulo" => "Results"
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              "identificador" => "sec0020"
              "titulo" => "A&#46; Vitamin D and non-melanoma skin cancer"
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                0 => array:2 [
                  "identificador" => "sec0025"
                  "titulo" => "Development of non-melanoma skin cancer"
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                  "identificador" => "sec0030"
                  "titulo" => "Effects of vitamin D supplementation on skin cancer"
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              "identificador" => "sec0035"
              "titulo" => "B&#46; Vitamin D and melanoma"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Development of melanoma"
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                1 => array:2 [
                  "identificador" => "sec0045"
                  "titulo" => "Vitamin D and melanoma prognosis"
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                2 => array:2 [
                  "identificador" => "sec0050"
                  "titulo" => "Vitamin D supplementation and melanoma risk"
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                3 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "Vitamin D and response to advanced therapy"
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                4 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Vitamin D and photoprotection"
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          "titulo" => "Discussion"
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          "titulo" => "Conflicts of interest"
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          "identificador" => "xack754569"
          "titulo" => "Acknowledgments"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2023-12-22"
    "fechaAceptado" => "2024-03-17"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Skin cancer"
            1 => "Squamous cell carcinoma"
            2 => "Melanoma"
            3 => "Vitamin D"
            4 => "Dermatology"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "C&#225;ncer cut&#225;neo"
            1 => "Carcinoma epidermoide"
            2 => "Melanoma"
            3 => "Vitamina D"
            4 => "Dermatolog&#237;a"
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Vitamin D &#40;VD&#41; deficiency has been associated with various tumors&#46; However&#44; the association between VD and skin cancer is controversial&#46; Although in non-melanoma skin cancer&#44; adequate or even high levels of VD can be associated with a higher risk of developing tumors&#44; this could be biased by the direct association between sun exposure and VD levels&#46; Regarding melanoma&#44; results are contradictory&#46; Most studies analyzed state that higher levels of VD could reduce the risk of melanoma&#44; be associated with melanomas with better prognosis and with an enhanced antitumor response&#44; and also with fewer adverse events associated with melanoma immunotherapy&#46; However&#44; prospective studies of adequate methodological quality are still needed to assess the association between VD levels and its supplementation and development&#47;prognosis in skin cancer&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La deficiencia de vitamina D &#40;VD&#41; se ha relacionado con diferentes tumores&#46; La asociaci&#243;n entre la VD y el c&#225;ncer cut&#225;neo es controvertida&#46; Para el c&#225;ncer cut&#225;neo no melanoma&#44; niveles adecuados o incluso elevados de VD podr&#237;an asociarse a un mayor riesgo tumoral&#44; aunque este hecho podr&#237;a estar sesgado por la asociaci&#243;n directa entre exposici&#243;n solar y niveles de VD&#46; En cuanto al melanoma&#44; hay resultados contradictorios&#46; La mayor&#237;a de los estudios analizados reportan que niveles m&#225;s altos de VD podr&#237;an disminuir el riesgo de melanoma&#44; podr&#237;an asociarse a melanomas con mejor pron&#243;stico y podr&#237;an correlacionarse con una mejor respuesta antitumoral y un menor perfil de efectos adversos en la inmunoterapia del melanoma&#46; Sin embargo&#44; son necesarios estudios prospectivos de adecuada calidad metodol&#243;gica que eval&#250;en la asociaci&#243;n de los niveles de VD y su suplementaci&#243;n&#44; y el desarrollo y pron&#243;stico del c&#225;ncer cut&#225;neo&#46;</p></span>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Vitamin D metabolism &#40;panel A&#41; and structure of activated vitamin D &#40;calcitriol or 1&#44;25-dihydroxycholecalciferol&#59; C27H44O3&#41; &#40;panel B&#41;&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel A&#46;</span> Vitamin D metabolism&#46; Vitamin D can be obtained through the diet&#44; or by cutaneous conversion via UVB&#44; which transforms provitamin D3 &#40;synthesized at skin level&#41; into previtamin D3&#46; The first hepatic step converts it to calcidiol or 25-hydroxyvitamin D through hepatic 25-hydroxylase&#46; The second step&#44; which occurs at renal level&#44; converts it into the active metabolite&#44; 1&#44;25-dihydroxycholecalciferol or calcitriol through renal 1-hydroxylase&#46; This mechanism is regulated&#44; among others&#44; by serum levels of calcium&#44; phosphorus&#44; and parathyroid hormone&#46; Calcitriol acts through intracellular vitamin D receptors &#40;VDR&#41;&#44; which activate the transcription and translation process of messenger RNA by synthesizing vitamin D-dependent proteins&#44; with their corresponding activity based on the target cell&#46; The excretion of vitamin D through bile is mediated by the activity of renal 24-hydroxylase&#44; which converts calcitriol into calcitroic acid&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel B</span>&#46; Structure of activated vitamin D&#46; Note that vitamin D must undergo 2 different hydroxylations to be activated&#58; activation &#35;1 &#40;green circle&#41; occurs in the liver forming 25-hydroxycholecalciferol&#44; or calcidiol&#59; activation &#35;2 &#40;red circle&#41; occurs in the kidney forming 1&#44;25-dihydroxycholecalciferol or calcitriol&#44; which is the active form&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; own elaboration and data obtained with permission from Navarro-Trivi&#241;o et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">5</span></a></p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CCL&#44; chemokine &#40;C-C motif&#41; ligand&#59; CD&#44; cluster of differentiation&#59; IL&#44; interleukin&#59; NLRP-3&#44; nucleotide-binding domain&#44; leucine-rich-containing family&#44; pyrin domain-containing-3&#59; ROS&#44; reactive oxygen species&#59; Th&#44; T helper lymphocyte &#40;collaborator&#41;&#59; TLR&#44; toll-like receptor&#59; TNF&#44; tumor necrosis factor&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Fantini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">3</span></a></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Biochemical action of vitamin D&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Implication at biochemical level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Possible clinical implications of vitamin D deficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of TLR2&#44; 4&#44; and 9 expression and signaling&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Regulation of the innate immune system&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="12" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Increased frequency of autoimmune diseases- Increased severity of autoimmune diseases- Increased frequency of certain infectious processes- Early development of cardiovascular disease&#58; obesity and arteriosclerosis- Earlier and more pronounced aging &#40;accelerated dermatoporosis&#44; sarcopenia&#44; etc&#46;&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in production of TNF-&#945;&#44; IL-1&#44; IL-6&#44; and IL-23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction of some cytokines that enhance the activity of T cells&#44; especially CD4<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased production of IL-4&#44; IL-5&#44; IL-10&#44; and CCL2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased production of anti-inflammatory cytokines&#44; regulating the activity of T cells&#44; especially Th17 and enhancing Th2 activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of IL-6 production&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduced Th17 activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inhibition of IL-33 production&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Reduced T cell and dendritic cell activity in some autoimmune diseases&#44; such as Guillain-Barr&#233; syndrome&#44; psoriasis&#44; or rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased production of Fox P3<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>regulatory T cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Reduced autoimmune T cell activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased lymphocyte co-stimulation via CD-28 molecule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Potential activity of cytotoxic T cells and activation of B cells under specific circumstances&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in generation of autoantibodies and ROS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fewer autoimmune cascades and inflammation control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increased levels of cathelicidin LL-37 and cationic protein AMP-18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fewer infections and early and adequate control of them&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Correct activation of TLR1&#44; 2&#44; and 8 response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fewer infections and early and adequate control of them&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Controlled increase in IL-1&#946; and defensin&#44; telomere shortening reduction&#44; increase in Nrf2 levels&#44; decrease in NF-k&#946; pathway&#44; decrease in NLRP-3 levels&#44; DNA damage reduction&#44; increase in mitochondrial biogenesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Regulation of cutaneous and systemic aging&#44; prevention of early and accelerated aging&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">Reduction of inflammation &#40;especially T cell response&#41;&#44; decrease in RAAS activation and ROS generation&#44; and control of plasma LDL levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prevention of arteriosclerosis&#44; obesity&#44; metabolic syndrome&#44; and early cardiovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Role of vitamin D in immunosurveillance and immunosenescence&#46;</p>"
        ]
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      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">25&#40;OH&#41;D&#44; 25-hydroxycholecalciferol&#59; BCC&#44; basal cell carcinoma&#59; cSCC&#44; cutaneous squamous cell carcinoma&#59; MA&#44; meta-analysis&#59; MSC&#44; melanoma skin cancer&#59; NMSC&#44; non-melanoma skin cancer&#59; RCT&#44; randomized clinical trial&#59; SC&#44; skin cancer&#59; SCC&#44; squamous cell carcinoma&#59; SR&#44; systematic review&#59; VD&#44; vitamin D &#40;no subtype specification&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Authors and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type&#44; methodology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van Dam et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">10</span></a> 2000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43 217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective&#44; multicenter cohorts- 8-year follow-up of patients with different dietary habits to evaluate the risk of breast cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Males between the ages of 40 and 75 years without a previous history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No significant correlation was found between the use or levels of 25VD and the appearance of BCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asgari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a> 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">440&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Retrospective&#44; single-center case-control study- Comparison of vitamin D levels between patients with BCC and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- All patients listed for BCC surgery-Healthy controls without dermatological diseases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- 25VD levels were significantly slightly higher in the BCC patient group vs the control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">12</span></a> 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1234&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective multicenter cohorts- 5-year follow-up of patients to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caucasian males &#8805; 65 years old of with or without prior history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25VD levels showed an inverse correlation with the history of SC and the risk of developing SC&#46; No correlation was found between VD intake and the history or occurrence of SC&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Phase III RCT &#40;<span class="elsevierStyleInterRef" id="intr0005" href="ctgov:NCT00000611">NCT00000611</span>&#41;&#46;- Development of SC in patients with supplementation of 1 g calcium and 400 IU of VD&#47;day vs placebo in a 7-year follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postmenopausal women with or without a previous history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The rates of SC occurrence in patients with supplementation did not differ from the control group&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Eide et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">14</span></a> 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3223&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Retrospective&#44; single-center&#44; cohort study- 8-year follow-up to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caucasian patients who underwent blood tests from 1997 through 2001 in the study of possible osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with non-insufficient 25VD levels &#40;&#62;15 ng&#47;mL&#41; had a significantly higher rate of NMSC&#44; especially in photo-exposed areas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">15</span></a> 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4641&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective multicentric cohort study- 18-year follow-up of patients to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nurses from the British NHS undergoing blood test from 1989 through 1990&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A positive and statistically significant correlation was found between 25VD levels and SC onset&#44; both MSC and NMSC&#46;Patients in the highest quartile &#40;highest 25VD levels&#41; had the highest risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van der Pols et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">16</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective multicentric cohort study- 8-year follow-up of patients to evaluate the occurrence of SC&#44; measuring 25VD levels before follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Healthy patients of any age and background who voluntarily participated in a SC prevention study from 1992 through 1996&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25VD levels &#62;<span class="elsevierStyleHsp" style=""></span>75 ng&#47;mL were associated with an increased risk of BCC&#44; while levels &#60; 75 ng&#47;mL were associated with increased risk of cSCC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">17</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2317&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR and MA- Cohorts&#44; case-control&#44; and cross-sectional studies with &#62;<span class="elsevierStyleHsp" style=""></span>10 patients were included&#44; which assessed the occurrence of SC based on 25VD levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset in relation to 25VD levels until January 2013 &#40;20 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated 25VD levels were associated with a higher risk of NMSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van Deventer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">18</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Cross sectional&#44; single-center- Measurement of 25VD levels in patients diagnosed with MSC or NMSC in a tertiary referral center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with MSC or NMSC during the summer of 2015 in a tertiary referral center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No association was ever found between 25VD levels and the occurrence of NMSC&#44; or between 25VD levels and previous history of NMSC&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Soares et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">241&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective&#44; single-center cases and control- Measurement of 25VD levels in patients diagnosed with BCC or cSCC in a tertiary referral center&#44; comparing them with healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A random group of NMSC-diagnosed patients from September 2016 through September 2017 regardless of age or history&#44; matched with healthy controls in a NMSC 5&#58;1 control ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Most of the sample &#40;both controls and NMSC patients&#41; had low or insufficient levels of 25VD- 25VD levels were significantly higher in patients with NMSC vs the control group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vojdeman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">212 244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Retrospective&#44; multicentric&#44; cohort study- Measurement of 25VD levels in a national population cohort and analysis of the incidence of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients collected in the Danish national registry who had documented 25VD levels from 2004 through 2010&#46; Incidence of SC was analyzed until 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated levels of 25VD were associated with a higher and statistically significant incidence of NMSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morgado-&#193;guila et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">6</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Prospective&#44; single-center cases and controls- Measurement of 25VD levels in patients diagnosed with BCC or cSCC&#44; comparing them with healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subjects diagnosed with cSCC or BCC in a tertiary referral center from 2015 through 2019 vs controls attending the clinic for a different reason &#40;unrelated to SC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It was significantly found that lower levels of 25VD were associated with a significantly lower incidence of NMSC&#46; Patients with values &#62;<span class="elsevierStyleHsp" style=""></span>18 ng&#47;mL had an up to 7 times higher risk of NMSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">21</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 067&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR and MA- All cohort&#44; clinical&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; clinical&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset until September 2020 &#40;24 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A direct association was found between 25VD levels and the risk of NMSC&#44; as well as between 25VD intake and the risk of NMSC&#46; This risk seemed more evident in observational than in clinical trials&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Abdelwahab et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">22</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>200 000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR- All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients assessing SC onset until January 2022 &#40;10 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It could not be concluded that normal&#44; elevated&#44; or low levels of 25VD are associated with a higher or lower risk of NMSC&#46; Great heterogeneity observed in the results of the included studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Main studies on the association of vitamin D and non-melanoma skin cancer&#46;</p>"
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      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">25VD&#44; 25-hydroxycholecalciferol&#59; BT&#44; Breslow thickness&#59; DFS&#44; disease-free survival&#59; GWAS&#44; Genome Wide Association Studies&#59; MA&#44; meta-analysis&#59; MSC&#44; melanoma skin cancer&#59; NMSC&#44; non-melanoma skin cancer&#59; RCT&#44; randomized clinical trial&#59; SC&#44; skin cancer&#59; SR&#44; systematic review&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Authors and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study type&#44; methodology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asgari et al&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a> 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68 611&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter retrospective cohort study-Patients followed in a study of supplementation with 25VD that analyzed the incidence of melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Participation in the Vitamins and Lifestyle cohort study analyzing tumor incidence in patients with various dietary supplements&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The supplementary intake of 25VD and its association with a lower incidence of melanoma was inconclusive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Newton-Bishop et al&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">25</span></a> 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">271&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective single-center case-control study-Patients diagnosed with melanoma in a tertiary referral center vs a control cohort of healthy patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma in a tertiary referral center from 2000 through 2005 were compared&#44; regardless of their background&#46;Patients were compared with a healthy control cohort from a melanoma registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-There was no significant reduction in the risk of melanoma in patients on 25VD supplements&#46;-Significantly higher levels of 25VD were associated with a lower risk of melanoma and a lower BT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36 282&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Phase III RCT &#40;<span class="elsevierStyleInterRef" id="intr0010" href="ctgov:NCT00000611">NCT00000611</span>&#41;-Development of SC in patients supplemented with 1g calcium and 400 IU of VD&#47;day vs placebo in a 7-year follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Postmenopausal women with or without a history of SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The rates of melanoma in patients on supplements did not differ from the control group without supplements&#46; However&#44; supplemented patients with a history of NMSC showed a significantly lower risk of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Van der Pols et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">16</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1191&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective multicenter cohort study- 8-year follow-up of patients to evaluate the occurrence of SC&#44; measuring the levels of 25VD before follow-up&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Healthy patients of any age and background who voluntarily participated in a SC prevention study from 1992 through 1996&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Levels of 25VD &#62;<span class="elsevierStyleHsp" style=""></span>75 ng&#47;mL were associated with a higher risk of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gambichler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">26</span></a> 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">764&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center&#44; cross-sectional study-Measurement of 25VD levels in patients at the time of melanoma diagnosis in a tertiary referral center&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with melanoma from 2009 through 2012&#44; comparing 25&#40;OH&#41;D levels and histological parameters and stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It was found that lower levels of 25VD &#40;&#8804; 30 ng&#47;mL&#41; were associated with a higher BT and a higher tumor stage&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Caini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">17</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1420&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-SR and MA-Included cohort and case-control&#44; cross-sectional study with &#62;<span class="elsevierStyleHsp" style=""></span>10 patients that evaluated the occurrence of SC based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies &#62;<span class="elsevierStyleHsp" style=""></span>10 patients evaluating SC occurrence until January 2013 &#40;20 articles&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No significant results associating 25VD levels and melanoma were found&#46; However&#44; a significant inverse relationship was found between BT and the levels of 25VD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bade et al&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">45</span></a> 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">465&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center&#44; case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma in a tertiary referral center with levels of 25VD on record&#44; vs a healthy control group from 2010 through 2013&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Deficiency &#40;&#8804; 20 ng&#47;mL&#41; of 25VD was more frequent in patients with melanoma vs controls&#46;- Lower levels of 25VD were associated with a higher BT and a lower specific melanoma survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Newton-Bishop et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">27</span></a> 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2182&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center&#44; cross-sectional&#44; prospective study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2001 through 2003&#46; Patients with positive lymph nodes and unknown primary were excluded&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower levels of 25VD are associated with melanoma of worse prognosis &#40;especially more ulcerated&#41; and higher specific mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Wyatt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">28</span></a> 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Cross-sectional&#44; single-center study-Measurement of 25VD levels in patients at the time of melanoma diagnosis&#44; followed by successive measurements at the follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with MSC from July 2010 through July 2011&#44; with comparisons between the levels of 25VD and the histological parameters of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Levels &#8804; 50 ng&#47;mL of 25VD were associated with an almost 4 times higher BT&#44; but not with a higher number of mitoses&#46;- Patients with levels of 25VD &#8805; 70 ng&#47;mL did not have lower incidence rates of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Saiag et al&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">29</span></a> 2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1171&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center&#44; cohort study-Measurement of 25VD levels in patients at the time of melanoma diagnosis&#44; followed by successive measurements at the follow-up&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All patients diagnosed with melanoma from 2003 through 2008 who agreed to initial and serial measurement of 25VD levels&#46; Follow-up was conducted until 2013&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Lower levels of 25VD were found in patients with higher BT&#44; ulceration&#44; or staging&#46;- The increase rate in these values did not improve specific melanoma prognosis or the overall survival for that matter&#44; suggesting that the initial value of 25VD levels may be biased by undetected or unanalyzed confounding factors&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Timerman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">30</span></a> 2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">252&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center&#44; cohort study-Measurement of 25VD levels in patients diagnosed with melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with MSC diagnosed from 2007 through 2013 who had their 25VD levels measured up to 1 year before or 1 year after diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Deficiency &#40;&#8804; 20 ng&#47;mL&#41; of 25VD was associated with a higher stage&#44; ulceration&#44; and mitotic index of melanoma&#46;- In patients with stage IV&#44; this deficiency was associated with worse specific melanoma prognosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">31</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center&#44; cross-sectional study-Measurement of 25VD levels in a cohort of patients diagnosed with melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2001 through 2013&#44; with measurements of 25VD levels up to 6 months after diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Direct association between low levels of 25VD and a higher BT&#44; more ulceration&#44; the desmoplastic subtype&#44; and the mitotic index&#46;- No relationship was ever found between 25VD levels and melanoma metastasis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipplaa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">32</span></a> 2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">341&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter&#44; cross-sectional study-Measurement of 25VD levels in a cohort of patients diagnosed with melanoma stage IIB-IIIC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma IIB-IIIC who were in a RCT with bevacizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- No relationship was ever found between 25VD levels and BT&#44; specific melanoma survival&#44; or overall survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vojdeman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">212 244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter&#44; retrospective&#44; cohort study-Measurement of 25VD levels in a national population cohort and analysis of the SC incidence rate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients were collected from the Danish national registry with documented 25VD levels from 2004 through 2010&#44; and the SC incidence rate was analyzed until 2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Elevated levels of 25VD were associated with a statistically significant and higher incidence of MSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cattaruza et al&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">33</span></a> 2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">236&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Ambispective&#44; single-center&#44; case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma with their 25VD levels on record vs a healthy control group collected subsequently&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A statistically significant association was found between insufficient &#40;20&#46;01-30 ng&#47;mL&#41; and deficient &#40;&#8804; 20 ng&#47;mL&#41; 25VD levels and the development of MSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tsai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">34</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 166&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- SR and MA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All cohort&#44; case-control&#44; and cross-sectional studies with &#62;<span class="elsevierStyleHsp" style=""></span>20 patients until November 2018 evaluating the relationship between melanoma and 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Patients with deficiency &#40;&#8804; 20 ng&#47;mL&#41; of 25VD had a higher incidence rate of melanoma&#46;- Positive correlation between BT and 25VD deficiency&#46;- Patients with 25VD deficiency had higher mortality rates from melanoma than patients with melanoma and levels &#62;<span class="elsevierStyleHsp" style=""></span>20 ng&#47;mL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Befon et al&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">35</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">198&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center case-control study-Measurement of 25VD levels in a cohort of patients with melanoma vs a healthy cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2011 through 2014 with 25VD levels on record and comparison between them and a control group from the same period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Patients with melanoma had lower mean levels of 25VD vs the control group &#40;25 vs 21 ng&#47;mL&#44; respectively&#41;&#46; - No association was ever found between 25VD levels and BT&#44; ulceration&#44; stage&#44; or type of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Stenehjem et al&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1416&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; multicenter&#44; case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma in a national Norwegian cohort&#46; They were matched with healthy controls from a different national cohort in the same country&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- It could not be statistically demonstrated that elevated or reduced levels of 25VD are associated with a higher or lower risk of melanoma&#44; although data suggest that probably the lower risk group is the one with levels between 30 ng&#47;mL and 50 ng&#47;mL&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lombardo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">279&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center case-control study-Measurement of 25VD levels in patients diagnosed with melanoma and comparison between them and healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma from 2016 through 2019 vs healthy controls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- Melanoma growth was more frequent in patients with 25VD deficiency &#40;&#8804; 30 ng&#47;mL&#41;&#46;- No significant association was ever found between 25VD levels and BT&#46; However&#44; lower levels of 25VD were reportedly associated with a higher mitotic index and a BT cutoff point &#62;<span class="elsevierStyleHsp" style=""></span>1 mm&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Johansson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a> 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Single-center RCT-Analysis of DFS in patients with stage II melanoma vs placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with stage II melanoma diagnosed from 2011 through 2015&#46; Supplementation with 25VD was compared to non-supplementation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- 25VD supplementation was not associated with better DFS rates vs non-supplementation&#46;- The combination of low levels of 25VD and BT &#8805; 3 mm reported lower rates of DFS which was not so for lower levels of 25VD&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moro et al&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">39</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">286&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center cohort study-Analysis of the incidence rate and characteristics of melanoma in a 25VD level-based cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma&#44; in whom 25VD levels were measured from 2011 through 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The combination of 25VD levels<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>BT <span class="elsevierStyleUnderline">&#62;</span><span class="elsevierStyleHsp" style=""></span>3 was associated with less DFS unlike lower levels of 25VD &#60;<span class="elsevierStyleHsp" style=""></span>9&#46;25 ng&#47;mL&#44; which were associated with more ulceration and lower overall survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gracia-Darder et al&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">264&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center cohort study-Analysis of the melanoma incidence rate and its characteristics in a 25VD level-based cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients diagnosed with melanoma&#44; in whom 25VD levels were measured from 1998 through 2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low levels of 25VD were associated with a higher BT&#44; lower specific melanoma survival&#44; and lower overall survival&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sha et al&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">41</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">411 436&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Multicenter&#44; cross-sectional study-Analysis of the association between VD supplementation and a lower melanoma risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients aged between 40 and 69 included in the English national registry&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Up to 21&#37; of the population had VD deficiency &#40;&#8804; 20&#41; and 34&#37; VD insufficiency &#40;&#8804; 30&#41;-Multivitamin supplementation was found to potentially reduce the risk of melanoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">42</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>500 000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Mendelian randomization analysis-Analysis of causal relationship between 25VD levels and melanoma&#44; with subsequent pleiotropy and sensitivity analysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">It included studies from the literature up to 2023 with which a GWAS could be conducted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive association between 25VD levels and melanoma&#44; even after conducting pleiotropy testing and sensitivity analysis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kanasuo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">43</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">498&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center&#44; cohort study-Healthy patients attending either oncological or non-oncological dermatological visits&#44; with their 25VD levels on record&#44; and in a subgroup&#44; with oral VD supplementation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients attending dermatological visits aged between 18 and 80 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">- No association was ever found between 25VD levels and the risk of melanoma&#46;- However&#44; 25VD supplementation was indeed associated with a lower risk of melanoma&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Shellenberger et al&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">44</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-SR and MA-14 case-control and prospective cohort studies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">All prospective cohort and case-control studies with &#62;<span class="elsevierStyleHsp" style=""></span>20 patients up until July 2022 were included&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher incidence rate of melanoma with 25VD deficiency &#40;&#8804; 30 ng&#47;mL&#41; and a higher BT with lower 25VD levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Main studies on the association of vitamin D and melanoma&#46;</p>"
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AE&#44; adverse events&#59; BRAF&#44; B-rapidly accelerated fibrosarcoma&#59; CTLA-4&#44; cytotoxic T-lymphocyte-associated protein 4&#59; MEK&#44; mitogen-activated protein kinase&#59; PD&#44; programmed cell death protein&#59; 25VD&#44; 25-hydroxycholecalciferol&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Authors and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type of study&#44; morphology&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Inclusion criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grover et al&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">47</span></a> 2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">213&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Retrospective&#44; single-center cohort study&#46;-Comparison of the colitis incidence rate in melanoma patients on immunotherapy based on supplementation or not with 25VD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with unresectable or metastatic melanoma on anti PD-1 or anti CTLA-4&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Supplementation with 25VD reduced the risk of immune-mediated colitis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reichrath et al&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">48</span></a> 2022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-Prospective&#44; single-center cohort study-Comparison of response to immunotherapy and targeted therapy in melanoma based on 25VD levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with unresectable or metastatic melanoma on BRAF&#47;MEK inhibitors or immunotherapy with anti-PD1&#46; Analysis of response and AE based on 25VD levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-25VD severe deficiency<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> was associated with a lower overall survival and progression-free survival&#44; and a higher tumor burden&#46;-Major AE in patients with 25VD levels &#8805; 10 ng&#47;mL and mutated BRAF&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Galus et al&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">54</span></a> 2023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2023 200&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-Non-randomized&#44; single center clinical trial-Comparison of immunotherapy response in melanoma based on vitamin D levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Patients diagnosed with unresectable melanoma on first-line therapy with anti PD1 &#40;nivolumab or pembrolizumab&#41;&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Patients with VD deficiency had a lower response rate&#44; lower progression-free survival&#44; and a lower overall survival vs those with normal levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Main studies on vitamin D and response to advanced therapy in melanoma&#46;</p>"
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ISSN: 00017310
Original language: English
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