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la enzima responsable de la conversi&#243;n de la vitamina D en su forma activa&#44; 1&#44;25-&#40;OH&#41;2D3&#44; que act&#250;a a nivel gen&#243;mico uni&#233;ndose al receptor VDR&#47;RXR y participando en m&#250;ltiples v&#237;as moleculares implicadas en la inmunomodulaci&#243;n&#44; la proliferaci&#243;n&#44; la diferenciaci&#243;n y la apoptosis celular<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">En las &#250;ltimas d&#233;cadas&#44; los an&#225;lisis epigen&#243;micos y transcript&#243;micos&#44; as&#237; como numerosos estudios experimentales en diferentes tipos de c&#225;ncer&#44; han aportado datos fiables que&#44; en conjunto&#44; indican una acci&#243;n protectora de la vitamina D frente a varios tipos de c&#225;ncer<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">3&#44;4</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">La vitamina D parece ejercer efectos antineopl&#225;sicos tanto directamente&#44; controlando la diferenciaci&#243;n&#44; proliferaci&#243;n y apoptosis de las c&#233;lulas neopl&#225;sicas&#44; como indirectamente&#44; regulando las c&#233;lulas estromales e inmunitarias del microambiente tumoral<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> y disminuyendo as&#237; el riesgo de met&#225;stasis<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#44;6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la deficiencia de vitamina D en la patog&#233;nesis tumoral sigue siendo controvertida&#46; Numerosos estudios han informado de la relaci&#243;n entre la deficiencia de vitamina D y el desarrollo de diferentes neoplasias&#44; con resultados contradictorios&#46; Los estudios epidemiol&#243;gicos observacionales mostraron que un estado bajo de vitamina D es un factor de riesgo para diferentes tipos de c&#225;ncer y sugieren que la suplementaci&#243;n con vitamina D3 podr&#237;a prevenir el desarrollo de c&#225;ncer&#46; Sin embargo&#44; los ensayos cl&#237;nicos controlados aleatorizados no han podido confirmar estos hallazgos para la poblaci&#243;n general<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Una revisi&#243;n de 2021 mostr&#243; que&#44; aunque los estudios observacionales indican en muchos casos que los niveles bajos de vitamina D se asocian a un mayor riesgo de c&#225;ncer&#44; los estudios aleatorizados muestran que la administraci&#243;n de suplementos vitam&#237;nicos reduce ligeramente la mortalidad total por c&#225;ncer&#44; pero no su incidencia<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">En nuestra experiencia&#44; la deficiencia de vitamina D se asoci&#243; con melanomas m&#225;s agresivos<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; Adem&#225;s&#44; en una revisi&#243;n sistem&#225;tica reciente&#44; la deficiencia de vitamina D&#44; definida con unos niveles<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; se ha asociado con un mayor grosor del Breslow y un peor pron&#243;stico en pacientes diagnosticados de melanoma y&#44; por el contrario&#44; no se asoci&#243; con una mayor incidencia de melanoma<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Se sabe que los pacientes que sobreviven a un melanoma tienen un mayor riesgo de desarrollar un segundo c&#225;ncer primario maligno no cut&#225;neo<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">En 2022&#44; un an&#225;lisis de 120&#44;299 pacientes de la base de datos SEER mostr&#243; una mayor incidencia de c&#225;nceres primarios secundarios &#40;CPS&#41; en pacientes con melanoma cut&#225;neo no acral&#44; melanoma lentiginoso acral&#44; melanoma mucoso y melanoma uveal en comparaci&#243;n con la poblaci&#243;n general<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">La evidencia de una asociaci&#243;n entre la deficiencia de vitamina D y el CPS no cut&#225;neo en pacientes diagnosticados de melanoma es incierta&#46; Por lo tanto&#44; creemos que esta cuesti&#243;n requiere m&#225;s investigaci&#243;n&#44; ya que no hay suficientes estudios que aporten pruebas cient&#237;ficas de que la deficiencia de vitamina D en el momento del diagn&#243;stico de melanoma sea un factor de riesgo para desarrollar segundas neoplasias malignas no cut&#225;neas&#46; As&#237; pues&#44; merece la pena analizar esta hip&#243;tesis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materiales y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Dise&#241;o del estudio</span><p id="par0055" class="elsevierStylePara elsevierViewall">Se realiz&#243; un estudio anal&#237;tico&#44; observacional&#44; longitudinal y retrospectivo basado en una cohorte de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022 en nuestro centro&#46; Los criterios de selecci&#243;n fueron pacientes adultos diagnosticados de melanoma con niveles de vitamina D disponibles e informaci&#243;n sobre el desarrollo o no de CPS no cut&#225;neo&#46; Toda la informaci&#243;n proced&#237;a de la base de datos del centro&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables de estudio</span><p id="par0060" class="elsevierStylePara elsevierViewall">La variable de resultado fue el desarrollo de un CPS no cut&#225;neo tras el diagn&#243;stico de un primer melanoma cut&#225;neo&#46; El CPS no cut&#225;neo se defini&#243; como el c&#225;ncer no cut&#225;neo que se hab&#237;a presentado dos o m&#225;s meses despu&#233;s del diagn&#243;stico de un melanoma&#46; Esta variable tambi&#233;n se consider&#243; como evento para estimar la incidencia acumulada y para ello se recuperaron de la base de datos la fecha de diagn&#243;stico del melanoma y la fecha de diagn&#243;stico del CPS&#46; Los pacientes que no desarrollaron un CPS fueron censurados en la fecha del &#250;ltimo seguimiento o muerte&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">La variable principal fue el nivel de vitamina D en el momento del diagn&#243;stico del melanoma&#44; definiendo tres categor&#237;as seg&#250;n su valor&#58; deficiente &#40;&#60;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; insuficiente &#40;10-29&#44;99<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; y normal &#40;30-100<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#46; En el estudio se incluyeron como covariables las siguientes caracter&#237;sticas&#58; sexo&#44; edad &#40;&#8804;60 o &#62;60 a&#241;os&#41;&#44; antecedentes familiares de melanoma&#44; antecedentes familiares de otro c&#225;ncer&#44; edad en el momento del diagn&#243;stico del melanoma primario y edad en el momento del diagn&#243;stico del CPS no cut&#225;neo&#44; estadio del melanoma &#40;I-II&#44; III-IV&#41;&#44; n&#250;mero de nevos &#40;&#60;20&#44; &#8805;20&#41;&#44; tipo histol&#243;gico &#40;lentigo maligno melanoma &#91;LMM&#93;&#44; melanoma de extensi&#243;n superficial &#91;MES&#93;&#44; melanoma nodular &#91;MN&#93;&#44; melanoma lentiginoso acral &#91;MLA&#93;&#41;&#44; antecedentes personales de otro c&#225;ncer no cut&#225;neo&#44; presencia de angiomas seniles&#44; antecedentes personales de c&#225;ncer de piel no melanoma &#40;carcinoma basocelular o escamoso&#41; y exposici&#243;n al sol &#40;&#8804;20 a&#241;os&#44; &#62;20 a&#241;os&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Metodolog&#237;a estad&#237;stica</span><p id="par0070" class="elsevierStylePara elsevierViewall">Para las variables continuas se utilizaron medidas de tendencia central&#44; como la media y la desviaci&#243;n est&#225;ndar o la mediana y el rango intercuart&#237;lico&#44; en funci&#243;n de su distribuci&#243;n&#46; En cambio&#44; para las variables categ&#243;ricas&#44; se utiliz&#243; el n&#250;mero absoluto de observaciones en cada categor&#237;a y su porcentaje sobre el n&#250;mero total de observaciones para determinar la distribuci&#243;n y la proporci&#243;n de la poblaci&#243;n&#46; Las diferencias entre las distribuciones de cada covariable seg&#250;n los grupos de pacientes se evaluaron mediante tablas de contingencia y&#44; como prueba de contraste&#44; la prueba <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> de Pearson o la prueba exacta de Fisher&#44; en su caso&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">La incidencia acumulada de desarrollo de un CPS se estim&#243; mediante el m&#233;todo de Kaplan-Meier&#44; y el an&#225;lisis univariante para cada variable se comprob&#243; mediante la prueba de rangos logar&#237;tmicos&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Se utilizaron modelos de regresi&#243;n de riesgos proporcionales &#40;PH&#41; de Cox univariantes y multivariantes para cuantificar la asociaci&#243;n entre las covariables y el desarrollo de un CPS no cut&#225;neo&#46; Todas las covariables con un valor p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;1 en los modelos univariantes se introdujeron en el an&#225;lisis multivariante por pasos hacia atr&#225;s&#46; Se consider&#243; un resultado estad&#237;sticamente significativo para un p-valor<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 en todas las pruebas&#46; El an&#225;lisis estad&#237;stico se realiz&#243; con IBM SPSS versi&#243;n 20&#46;0&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0085" class="elsevierStylePara elsevierViewall">El estudio incluy&#243; a 663 pacientes&#44; 34 de los cuales desarrollaron un CPS no cut&#225;neo tras el diagn&#243;stico de melanoma&#46; Entre los pacientes hab&#237;a 361 &#40;54&#44;4&#37;&#41; hombres y 302 &#40;45&#44;6&#37;&#41; mujeres&#46; La mediana de edad en el momento del diagn&#243;stico fue de 61 a&#241;os &#40;rango intercuart&#237;lico<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48-72 a&#241;os&#41;&#46; 46 &#40;6&#44;9&#37;&#41; pacientes presentaban unos niveles deficientes de vitamina D&#44; y 449 &#40;67&#44;7&#37;&#41; niveles insuficientes&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Quinientos sesenta y un pacientes &#40;84&#44;6&#37;&#41; presentaban un melanoma localizado &#40;estadios 0&#44; I y II&#41; y 102 &#40;15&#44;4&#37;&#41; ten&#237;an met&#225;stasis en el momento del diagn&#243;stico &#40;estadios III o IV&#41;&#46; Se objetivaron m&#225;s de 50 angiomas seniles en 26 pacientes &#40;4&#44;2&#37;&#41;&#44; y antecedentes personales de c&#225;ncer de piel no melanoma en 95 de los pacientes &#40;4&#44;4&#37;&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se detallan las caracter&#237;sticas de la poblaci&#243;n y las tablas de contingencia de los grupos de estudio&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Al analizar la distribuci&#243;n de las variables independientes estudiadas en los grupos definidos por la presencia o ausencia de un CPS no cut&#225;neo&#44; encontramos que el grupo que hab&#237;a desarrollado un CPS no cut&#225;neo ten&#237;a una proporci&#243;n significativamente mayor de pacientes mayores de 60 a&#241;os &#40;76&#44;5&#37; frente a 50&#44;4&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#41; y pacientes con 20 o menos nevos &#40;76&#44;5&#37; frente a 59&#44;5&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;049&#41;&#44; y una tendencia a presentar un melanoma nodular &#40;26&#44;5&#37; frente a 14&#44;9&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;071&#41; y un estadio avanzado &#40;III&#47;IV&#41; &#40;26&#44;5&#37; frente a 14&#44;8&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;066&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">No se encontraron diferencias estad&#237;sticamente significativas para las variables sexo&#44; niveles de vitamina D&#44; antecedentes personales de c&#225;ncer&#44; tipo histol&#243;gico&#44; antecedentes familiares de melanoma&#44; antecedentes familiares de c&#225;ncer&#44; exposici&#243;n solar&#44; angiomas seniles y antecedentes de carcinoma basocelular o epidermoide&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">An&#225;lisis de la incidencia acumulada</span><p id="par0110" class="elsevierStylePara elsevierViewall">Tras una mediana de seguimiento de 51&#44;3 meses&#44; 34 &#40;5&#44;1&#37;&#41; pacientes desarrollaron un CPS no cut&#225;neo&#46; La <a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> muestra que la incidencia esetimada global de CPS no cut&#225;neo a los cinco a&#241;os del 6&#44;1&#37;&#44; y a los diez a&#241;os&#44; del 8&#44;7&#37;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">En el an&#225;lisis estad&#237;stico univariante&#44; la incidencia acumulada estimada a 5 y 10 a&#241;os de CPS no cut&#225;neo fue del 9&#44;2&#37; para los pacientes con niveles deficientes de vitamina D&#44; del 6&#44;1&#37; y 8&#44;7&#37; para los pacientes con unos niveles insuficientes&#44; respectivamente&#44; y del 5&#44;4 y 8&#44;9&#37; en los pacientes con unos niveles suficientes&#44; respectivamente&#44; mostrando que los niveles de vitamina D no difer&#237;an significativamente en el tiempo de supervivencia para el desarrollo de un CPS no cut&#225;neo &#40;log-rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;817&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>a&#41;&#46; Entre las variables restantes&#44; se observaron diferencias significativas para la edad&#44; el n&#250;mero de nevos&#44; el melanoma nodular y el estadio III&#47;IV &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Los pacientes mayores de 60 a&#241;os tuvieron una incidencia significativamente mayor de un CPS no cut&#225;neo &#40;log rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En los pacientes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; la incidencia acumulada a los 5 y 10 a&#241;os fue del 9&#44;6&#37; y el 13&#44;9&#37;&#44; respectivamente&#46; Y del 2&#44;8&#37; y el 3&#44;9&#37; para los pacientes<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>b&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">En cuanto a la presencia de melanoma nodular &#40;log-rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;025&#41;&#44; la incidencia en los pacientes con un melanoma nodular fue del 8&#44;9&#37; a los cinco a&#241;os y del 14&#44;6&#37; a los diez a&#241;os&#44; mientras que los pacientes sin melanoma nodular tuvieron una incidencia acumulada a los 5 y 10 a&#241;os del 5&#44;6&#37; y el 7&#44;8&#37;&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>c&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Respecto al estadio &#40;log rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;025&#41;&#44; los pacientes con estadio III&#47;IV tuvieron una incidencia acumulada a los 5 y 10 a&#241;os del 11&#44;1&#37; y el 17&#44;9&#37;&#44; respectivamente&#46; Por el contrario&#44; los pacientes con estadio 0&#47;I&#47;II tuvieron una incidencia acumulada a los 5 a&#241;os del 5&#44;3&#37; y del 7&#44;5&#37; a los diez a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>d&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Tras el an&#225;lisis multivariable de riesgos proporcionales de Cox&#44; s&#243;lo la edad<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os &#40;HR 3&#44;4&#59; IC 95&#37; HR 1&#44;5-7&#44;6&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; y el melanoma nodular &#40;HR 2&#44;2&#59; IC 95&#37; HR 1&#44;0-4&#44;8&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;038&#41; mantuvieron su asociaci&#243;n significativa con el desarrollo de un CPS no cut&#225;neo &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0140" class="elsevierStylePara elsevierViewall">Hemos realizado un estudio anal&#237;tico&#44; observacional&#44; longitudinal y retrospectivo basado en una cohorte de 663 pacientes diagnosticados de melanoma para evaluar la relaci&#243;n entre los niveles de vitamina D medidos en el momento del diagn&#243;stico y el desarrollo de una segunda neoplasia maligna no cut&#225;nea&#46; Los resultados han demostrado que la deficiencia de vitamina D en el momento del diagn&#243;stico de melanoma no aumenta el riesgo de desarrollar una segunda neoplasia maligna no cut&#225;nea&#46; Sin embargo&#44; analizando diferentes variables como el sexo&#44; la edad&#44; los antecedentes de melanoma y otras neoplasias&#44; hemos observado que presentar el melanoma a una edad superior a los 60 a&#241;os y el subtipo de melanoma nodular se asocian a un mayor riesgo de desarrollar segundas neoplasias malignas no cut&#225;neas&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Aunque algunos estudios hab&#237;an asociado previamente una menor edad en el momento del diagn&#243;stico del melanoma con un mayor riesgo de desarrollar segundos c&#225;nceres primarios<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a>&#44; numerosos estudios recientes han demostrado que una mayor edad aumenta el riesgo de m&#250;ltiples tumores primarios&#44; Adam C&#46; Krajewski et al&#46; realizaron un estudio prospectivo en 222 pacientes de edad &#62; o &#61; 65 a&#241;os diagnosticados de melanoma y observaron que&#44; tras una mediana de seguimiento de 5 a&#241;os&#44; alrededor del 10&#37; desarrollaron un segundo melanoma&#44; y el 4&#37; desarrollaron tres o m&#225;s melanomas&#44; lo que pone de manifiesto la importancia de un seguimiento estrecho en estos pacientes<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a>&#46; En nuestro estudio&#44; la edad superior a 60 a&#241;os se asoci&#243; de forma estad&#237;sticamente significativa con un aumento de otros tumores primarios no cut&#225;neos&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">La relaci&#243;n entre el envejecimiento y la incidencia de c&#225;ncer est&#225; bien establecida&#44; y el envejecimiento representa uno de los factores de riesgo m&#225;s cr&#237;ticos para el desarrollo de tumores&#46; Esta edad y el c&#225;ncer comparten algunos mecanismos biol&#243;gicos complejos&#44; como la inestabilidad gen&#243;mica con una acumulaci&#243;n progresiva de da&#241;o gen&#233;tico&#44; unas alteraciones epigen&#233;ticas &#40;debidas principalmente a la exposici&#243;n prolongada a carcin&#243;genos ambientales&#41; y un debilitamiento progresivo de los mecanismos de oncosupresi&#243;n vinculados a la inmunosenescencia<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">15&#44;16</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">La asociaci&#243;n entre el melanoma nodular y el riesgo de segundas neoplasias cut&#225;neas malignas es un hallazgo incidental e inesperado en nuestro estudio&#46; El melanoma nodular es&#44; por definici&#243;n histol&#243;gica&#44; un subtipo de melanoma que no muestra una fase de crecimiento radial y no muestra proliferaci&#243;n melanoc&#237;tica intrad&#233;rmica m&#225;s all&#225; de tres crestas epid&#233;rmicas en cada margen de la masa tumoral<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a>&#46; El melanoma nodular se ha asociado a un peor pron&#243;stico debido a un grosor de Breslow generalmente mayor en el momento del diagn&#243;stico&#46; Presenta procesos biol&#243;gicos intr&#237;nsecamente m&#225;s agresivos que el melanoma de extensi&#243;n superficial<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Desde un punto de vista molecular&#44; el melanoma nodular muestra una mayor frecuencia de mutaci&#243;n en <span class="elsevierStyleItalic">NRAS</span> que el melanoma de extensi&#243;n superficial&#44; aunque no se han demostrado diferencias en la tasa de mutaci&#243;n <span class="elsevierStyleItalic">BRAF</span> en este subtipo de melanoma&#46; Adem&#225;s&#44; el MN parece mostrar una menor prevalencia de genes som&#225;ticos mutados que el MES<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; El melanoma nodular tambi&#233;n muestra una mayor frecuencia de mutaciones en el promotor de <span class="elsevierStyleItalic">TERT</span> que otros subtipos<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Dado que los pacientes con un melanoma nodular tienen una tasa de mortalidad m&#225;s elevada&#44; cabr&#237;a esperar que el riesgo de segundas neoplasias malignas se redujera en este subgrupo de pacientes debido a la menor tasa de supervivencia&#46; Sin embargo&#44; en un estudio de 2022&#44; Yen T&#46; Luu et al&#46;&#44; utilizando la base de datos Surveillance&#44; Epidemiology&#44; and End Results &#40;SEER&#41;&#44; demostraron que los supervivientes de MN&#44; en comparaci&#243;n con otros histotipos&#44; ten&#237;an un riesgo un 27&#37; mayor de desarrollar segundas neoplasias malignas primarias<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a>&#46; Este resultado parece coincidir con el nuestro&#44; pero actualmente faltan m&#225;s datos de apoyo en la literatura&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Las posibles causas son muchas y a&#250;n est&#225;n por dilucidar&#46; La susceptibilidad gen&#233;tica individual puede desempe&#241;ar un papel importante en la predisposici&#243;n a estos tumores&#44; al igual que los factores de riesgo ambientales o inmunol&#243;gicos&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; los pacientes con MN tienden a tener tumores m&#225;s gruesos y&#44; por tanto&#44; una mayor tasa de tratamiento que los pacientes con otros tipos de melanoma&#46; No se puede excluir que la terapia pueda desempe&#241;ar un papel importante en el desarrollo de un CPS&#59; sin embargo&#44; en este estudio no se recogieron datos sobre la terapia de los pacientes&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Algunas limitaciones y puntos fuertes del presente estudio merecen consideraci&#243;n&#46; En primer lugar&#44; nuestro estudio incluye datos de un &#250;nico centro&#44; por lo que la poblaci&#243;n estudiada puede no representar a la poblaci&#243;n general&#46; Adem&#225;s&#44; la muestra analizada es num&#233;ricamente limitada&#44; ya que considera 663 pacientes&#44; de los cuales s&#243;lo 34 desarrollaron una segunda neoplasia primaria&#46; En segundo lugar&#44; dado que los valores de vitamina D se recogieron durante un periodo relativamente corto&#44; el tiempo de seguimiento de los pacientes tambi&#233;n es limitado &#40;51&#44;3 meses de media&#41;&#46; En cuanto a los niveles de vitamina D&#44; se utilizaron los rangos establecidos para el metabolismo &#243;seo&#44; pero &#233;stos podr&#237;an variar en funci&#243;n del desarrollo tumoral&#46; No se realiz&#243; un an&#225;lisis del punto de corte de vitamina D&#46; Otra limitaci&#243;n de nuestro estudio es la falta de caracterizaci&#243;n del tipo de neoplasias primarias secundarias desarrolladas por los pacientes&#46; Por &#250;ltimo&#44; en cuanto a la correlaci&#243;n entre un CPS no cut&#225;neo y el melanoma nodular&#44; al tratarse de un hallazgo incidental e inesperado&#44; no tuvimos en cuenta otras variables&#44; como las caracter&#237;sticas moleculares&#44; el sustrato gen&#233;tico y las terapias actuales de estos pacientes&#44; que podr&#237;an aportar informaci&#243;n importante y que representan hasta la fecha un campo inexplorado digno de mayor estudio&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Por otro lado&#44; el hecho de que los datos se obtuvieran prospectivamente de un &#250;nico centro&#44; con valores analizados por el mismo laboratorio&#44; hizo posible la obtenci&#243;n de una colecci&#243;n de datos homog&#233;nea&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; seg&#250;n nuestro estudio&#44; la deficiencia de vitamina D no se asocia a un mayor riesgo de desarrollar un CPS no cut&#225;neo en pacientes con melanoma&#46; Al mismo tiempo&#44; la edad superior a 60 a&#241;os y el melanoma nodular parecen tener un valor predictivo positivo para desarrollar un CPS no cut&#225;neo&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Se necesitan m&#225;s estudios para caracterizar la relaci&#243;n entre el MN y el CPS no cut&#225;neo y para comprender los complejos mecanismos biol&#243;gicos subyacentes&#46; No obstante&#44; nuestros datos confirman la importancia de un seguimiento estrecho de estos pacientes&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicto de intereses</span><p id="par0200" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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              "titulo" => "An&#225;lisis de la incidencia acumulada"
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    "fechaRecibido" => "2023-08-05"
    "fechaAceptado" => "2023-10-08"
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          "palabras" => array:4 [
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            1 => "Melanoma"
            2 => "Segundos canceres primarios"
            3 => "Melanoma nodular"
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            0 => "Vitamin D"
            1 => "Melanoma"
            2 => "Second primary cancer"
            3 => "Nodular melanoma"
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    "resumen" => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Antecedentes</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El d&#233;ficit de vitamina D se asocia con un mayor riesgo de padecer varias enfermedades&#44; incluido el c&#225;ncer&#46; Molecularmente&#44; esta parece tener un efecto antineopl&#225;sico&#46; Sin embargo&#44; el papel que juega en la patog&#233;nesis del c&#225;ncer no est&#225; bien esclarecido y hay resultados dispares en los estudios publicados&#46; El objetivo del presente fue determinar si unos niveles de vitamina D deficientes en el momento del diagn&#243;stico del melanoma aumentaba el riesgo de desarrollar un c&#225;ncer no cut&#225;neo &#40;CNC&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material y m&#233;todo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se dise&#241;&#243; un estudio retrospectivo de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022&#46; El efecto de cada una de las variables seleccionadas en el desarrollo de un CNC durante el seguimiento tras el diagn&#243;stico del melanoma se realiz&#243; mediante el estudio de supervivencia con el m&#233;todo de Kaplan-Meier y las diferencias se evaluaron con la prueba de los rangos logar&#237;tmicos&#46; Se elaboraron modelos uni y multivariados de riesgos proporcionales de Cox para cuantificar el efecto de cada valor de las variables de estudio en el tiempo para desarrollar un CNC&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">De los 663 pacientes&#44; 34 desarrollaron un CNC tras el melanoma&#46; No hubo diferencias estad&#237;sticamente significativas entre los grupos definidos por los niveles de vitamina D &#40;<span class="elsevierStyleItalic">log-rank</span>&#44; p &#61; 0&#44;761&#41;&#46; Sin embargo&#44; una edad &#62; 60&#44; el estadio III&#47;IV&#44; y el tipo nodular se asociaron significativamente al desarrollo de un CNC&#46; Tras el an&#225;lisis multivariado&#44; solo la edad &#62; 60 &#40;<span class="elsevierStyleItalic">hazard ratio</span> &#91;HR&#93; 3&#44;4&#59; intervalo de confianza &#91;IC&#93; 95&#37; HR&#58;1&#44;5-7&#44;6&#41; y el subtipo nodular de melanoma &#40;HR 2&#44;2&#59; IC 95&#37; HR&#58;1&#44;0-4&#44;8&#41; se mantuvieron en el modelo predictivo final&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Nuestros resultados sugieren que unos niveles de vitamina D deficientes en el diagn&#243;stico de melanoma no se asocian a un mayor riesgo de desarrollar un CNC&#46; Sin embargo&#44; en una edad &#62; 60 y el subtipo nodular s&#237; que aumentan el riesgo de desarrollar un CNC&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Vitamin D deficiency associates with the risk of developing many diseases&#44; including cancer&#46; At the molecular level&#44; vitamin D appears to have an antineoplastic effect&#46; However&#44; the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results&#46; This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers &#40;SPC&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materials and methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022&#46; The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan&#8211;Meier curves and differences were assessed by log-rank tests&#46; Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Out of 663 patients&#44; 34 developed a non-cutaneous SPC&#46; There was no statistically significant association between vitamin D levels and non-cutaneous SPC development &#40;log-rank&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;761&#41;&#46; Age<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 years&#44; stage III&#47;IV&#44; and nodular melanoma subtype were significantly associated with the development of a SPC&#46; After multivariate analysis&#44; only age<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 years &#40;HR 3&#46;4&#59; HR CI 95&#37;&#58; 1&#46;5&#8211;7&#46;6&#41; and nodular melanoma subtype &#40;HR 2&#46;2&#59; HR CI 95&#37;&#58; 1&#46;0&#8211;4&#46;8&#41; were included in the final model&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients&#46; However&#44; age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development&#46;</p></span>"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Curva de Kaplan-Meier que representa la incidencia acumulada global de CPS no cut&#225;neo en pacientes con melanoma&#46;</p>"
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Curva de Kaplan-Meier que representa la incidencia acumulada estimada de CPS no cut&#225;neo por niveles de vitamina D &#40;a&#41;&#44; edad &#40;b&#41;&#44; melanoma nodular &#40;c&#41; y estadio &#40;d&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&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">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleItalic">N</span>&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
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                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Edad &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8804;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">320&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">312&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;003</span>&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"><span class="elsevierStyleHsp" style=""></span>&#62;60&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">343&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">317&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hombre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">361&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;374</span>&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"><span class="elsevierStyleHsp" style=""></span>Mujer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">302&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">52&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Niveles de Vitamina D &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Deficiente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;761</span>&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"><span class="elsevierStyleHsp" style=""></span>Insuficiente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">449&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">425&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&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"><span class="elsevierStyleHsp" style=""></span>Normal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">168&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes personales de c&#225;ncer &#40;v&#46;p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">594&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Melanoma Nodular &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes familiares de melanoma &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">6&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">593&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">560&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;170</span>&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"><span class="elsevierStyleHsp" style=""></span>Si&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes familiares de c&#225;ncer &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">307&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;292</span>&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"><span class="elsevierStyleHsp" style=""></span>Si&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">346&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">325&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de nevus &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">22&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">387&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">361&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;049</span>&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"><span class="elsevierStyleHsp" style=""></span>&#8805;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">254&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">246&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exposici&#243;n al sol &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">18&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>&#8804;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">573&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">543&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;909</span>&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"><span class="elsevierStyleHsp" style=""></span>&#62;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#44;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Estadio de la enfermedad &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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">561&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">536&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>III&#47;IV&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">102&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">14&#44;8&nbsp;\t\t\t\t\t\t\n
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El melanoma de tipo nodular pero no los niveles de vitamina D aumenta el riesgo de desarrollar una segunda neoplasia no cutánea en pacientes con un melanoma: estudio observacional de 663 pacientes
Nodular Type but Not Vitamin D Levels Increases the Risk of Second Primary Cancers in Melanoma Patients: An Observational Study of 663 Patients
A. Massaa,1, A. Isasi-Fusterb,1, C. Requenac, E. Manrique-Silvac, R. Kumard,e, E. Nagoreb,c,
Corresponding author
eduardo.nagore@ucv.es
enagore@fivo.org

Autor para correspondencia.
a Section of Dermatology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy
b Facultad de Medicina, Universidad Católica de Valencia San Vicente Mártir, València, Spain
c Servicio de Dermatología, Fundación Instituto Valenciano de Oncología, València, Spain
d Institute of Medical Biometry, University of Heidelberg, Heidelberg, Germany
e Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El papel de la vitamina D en el metabolismo del calcio y la homeostasis &#243;sea es conocido y su deficiencia es causa de raquitismo y osteoporosis&#46; La deficiencia de vitamina D se asocia con el riesgo de desarrollar m&#250;ltiples patolog&#237;as&#44; ya que puede causar enfermedades cardiovasculares&#44; esclerosis m&#250;ltiple&#44; artritis reumatoide&#44; diabetes mellitus tipo I y c&#225;ncer<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">La mayor&#237;a de las c&#233;lulas nucleadas expresan el receptor de la vitamina D&#46; Numerosos tejidos&#44; adem&#225;s del ri&#241;&#243;n&#44; expresan 1-alfa-hidroxilasa&#44; la enzima responsable de la conversi&#243;n de la vitamina D en su forma activa&#44; 1&#44;25-&#40;OH&#41;2D3&#44; que act&#250;a a nivel gen&#243;mico uni&#233;ndose al receptor VDR&#47;RXR y participando en m&#250;ltiples v&#237;as moleculares implicadas en la inmunomodulaci&#243;n&#44; la proliferaci&#243;n&#44; la diferenciaci&#243;n y la apoptosis celular<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">En las &#250;ltimas d&#233;cadas&#44; los an&#225;lisis epigen&#243;micos y transcript&#243;micos&#44; as&#237; como numerosos estudios experimentales en diferentes tipos de c&#225;ncer&#44; han aportado datos fiables que&#44; en conjunto&#44; indican una acci&#243;n protectora de la vitamina D frente a varios tipos de c&#225;ncer<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">3&#44;4</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">La vitamina D parece ejercer efectos antineopl&#225;sicos tanto directamente&#44; controlando la diferenciaci&#243;n&#44; proliferaci&#243;n y apoptosis de las c&#233;lulas neopl&#225;sicas&#44; como indirectamente&#44; regulando las c&#233;lulas estromales e inmunitarias del microambiente tumoral<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> y disminuyendo as&#237; el riesgo de met&#225;stasis<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">4&#44;6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Sin embargo&#44; la deficiencia de vitamina D en la patog&#233;nesis tumoral sigue siendo controvertida&#46; Numerosos estudios han informado de la relaci&#243;n entre la deficiencia de vitamina D y el desarrollo de diferentes neoplasias&#44; con resultados contradictorios&#46; Los estudios epidemiol&#243;gicos observacionales mostraron que un estado bajo de vitamina D es un factor de riesgo para diferentes tipos de c&#225;ncer y sugieren que la suplementaci&#243;n con vitamina D3 podr&#237;a prevenir el desarrollo de c&#225;ncer&#46; Sin embargo&#44; los ensayos cl&#237;nicos controlados aleatorizados no han podido confirmar estos hallazgos para la poblaci&#243;n general<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Una revisi&#243;n de 2021 mostr&#243; que&#44; aunque los estudios observacionales indican en muchos casos que los niveles bajos de vitamina D se asocian a un mayor riesgo de c&#225;ncer&#44; los estudios aleatorizados muestran que la administraci&#243;n de suplementos vitam&#237;nicos reduce ligeramente la mortalidad total por c&#225;ncer&#44; pero no su incidencia<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">En nuestra experiencia&#44; la deficiencia de vitamina D se asoci&#243; con melanomas m&#225;s agresivos<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">8&#44;9</span></a>&#46; Adem&#225;s&#44; en una revisi&#243;n sistem&#225;tica reciente&#44; la deficiencia de vitamina D&#44; definida con unos niveles<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; se ha asociado con un mayor grosor del Breslow y un peor pron&#243;stico en pacientes diagnosticados de melanoma y&#44; por el contrario&#44; no se asoci&#243; con una mayor incidencia de melanoma<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Se sabe que los pacientes que sobreviven a un melanoma tienen un mayor riesgo de desarrollar un segundo c&#225;ncer primario maligno no cut&#225;neo<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">En 2022&#44; un an&#225;lisis de 120&#44;299 pacientes de la base de datos SEER mostr&#243; una mayor incidencia de c&#225;nceres primarios secundarios &#40;CPS&#41; en pacientes con melanoma cut&#225;neo no acral&#44; melanoma lentiginoso acral&#44; melanoma mucoso y melanoma uveal en comparaci&#243;n con la poblaci&#243;n general<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">La evidencia de una asociaci&#243;n entre la deficiencia de vitamina D y el CPS no cut&#225;neo en pacientes diagnosticados de melanoma es incierta&#46; Por lo tanto&#44; creemos que esta cuesti&#243;n requiere m&#225;s investigaci&#243;n&#44; ya que no hay suficientes estudios que aporten pruebas cient&#237;ficas de que la deficiencia de vitamina D en el momento del diagn&#243;stico de melanoma sea un factor de riesgo para desarrollar segundas neoplasias malignas no cut&#225;neas&#46; As&#237; pues&#44; merece la pena analizar esta hip&#243;tesis&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materiales y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Dise&#241;o del estudio</span><p id="par0055" class="elsevierStylePara elsevierViewall">Se realiz&#243; un estudio anal&#237;tico&#44; observacional&#44; longitudinal y retrospectivo basado en una cohorte de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022 en nuestro centro&#46; Los criterios de selecci&#243;n fueron pacientes adultos diagnosticados de melanoma con niveles de vitamina D disponibles e informaci&#243;n sobre el desarrollo o no de CPS no cut&#225;neo&#46; Toda la informaci&#243;n proced&#237;a de la base de datos del centro&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Variables de estudio</span><p id="par0060" class="elsevierStylePara elsevierViewall">La variable de resultado fue el desarrollo de un CPS no cut&#225;neo tras el diagn&#243;stico de un primer melanoma cut&#225;neo&#46; El CPS no cut&#225;neo se defini&#243; como el c&#225;ncer no cut&#225;neo que se hab&#237;a presentado dos o m&#225;s meses despu&#233;s del diagn&#243;stico de un melanoma&#46; Esta variable tambi&#233;n se consider&#243; como evento para estimar la incidencia acumulada y para ello se recuperaron de la base de datos la fecha de diagn&#243;stico del melanoma y la fecha de diagn&#243;stico del CPS&#46; Los pacientes que no desarrollaron un CPS fueron censurados en la fecha del &#250;ltimo seguimiento o muerte&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">La variable principal fue el nivel de vitamina D en el momento del diagn&#243;stico del melanoma&#44; definiendo tres categor&#237;as seg&#250;n su valor&#58; deficiente &#40;&#60;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; insuficiente &#40;10-29&#44;99<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; y normal &#40;30-100<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#46; En el estudio se incluyeron como covariables las siguientes caracter&#237;sticas&#58; sexo&#44; edad &#40;&#8804;60 o &#62;60 a&#241;os&#41;&#44; antecedentes familiares de melanoma&#44; antecedentes familiares de otro c&#225;ncer&#44; edad en el momento del diagn&#243;stico del melanoma primario y edad en el momento del diagn&#243;stico del CPS no cut&#225;neo&#44; estadio del melanoma &#40;I-II&#44; III-IV&#41;&#44; n&#250;mero de nevos &#40;&#60;20&#44; &#8805;20&#41;&#44; tipo histol&#243;gico &#40;lentigo maligno melanoma &#91;LMM&#93;&#44; melanoma de extensi&#243;n superficial &#91;MES&#93;&#44; melanoma nodular &#91;MN&#93;&#44; melanoma lentiginoso acral &#91;MLA&#93;&#41;&#44; antecedentes personales de otro c&#225;ncer no cut&#225;neo&#44; presencia de angiomas seniles&#44; antecedentes personales de c&#225;ncer de piel no melanoma &#40;carcinoma basocelular o escamoso&#41; y exposici&#243;n al sol &#40;&#8804;20 a&#241;os&#44; &#62;20 a&#241;os&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Metodolog&#237;a estad&#237;stica</span><p id="par0070" class="elsevierStylePara elsevierViewall">Para las variables continuas se utilizaron medidas de tendencia central&#44; como la media y la desviaci&#243;n est&#225;ndar o la mediana y el rango intercuart&#237;lico&#44; en funci&#243;n de su distribuci&#243;n&#46; En cambio&#44; para las variables categ&#243;ricas&#44; se utiliz&#243; el n&#250;mero absoluto de observaciones en cada categor&#237;a y su porcentaje sobre el n&#250;mero total de observaciones para determinar la distribuci&#243;n y la proporci&#243;n de la poblaci&#243;n&#46; Las diferencias entre las distribuciones de cada covariable seg&#250;n los grupos de pacientes se evaluaron mediante tablas de contingencia y&#44; como prueba de contraste&#44; la prueba <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> de Pearson o la prueba exacta de Fisher&#44; en su caso&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">La incidencia acumulada de desarrollo de un CPS se estim&#243; mediante el m&#233;todo de Kaplan-Meier&#44; y el an&#225;lisis univariante para cada variable se comprob&#243; mediante la prueba de rangos logar&#237;tmicos&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Se utilizaron modelos de regresi&#243;n de riesgos proporcionales &#40;PH&#41; de Cox univariantes y multivariantes para cuantificar la asociaci&#243;n entre las covariables y el desarrollo de un CPS no cut&#225;neo&#46; Todas las covariables con un valor p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;1 en los modelos univariantes se introdujeron en el an&#225;lisis multivariante por pasos hacia atr&#225;s&#46; Se consider&#243; un resultado estad&#237;sticamente significativo para un p-valor<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05 en todas las pruebas&#46; El an&#225;lisis estad&#237;stico se realiz&#243; con IBM SPSS versi&#243;n 20&#46;0&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0085" class="elsevierStylePara elsevierViewall">El estudio incluy&#243; a 663 pacientes&#44; 34 de los cuales desarrollaron un CPS no cut&#225;neo tras el diagn&#243;stico de melanoma&#46; Entre los pacientes hab&#237;a 361 &#40;54&#44;4&#37;&#41; hombres y 302 &#40;45&#44;6&#37;&#41; mujeres&#46; La mediana de edad en el momento del diagn&#243;stico fue de 61 a&#241;os &#40;rango intercuart&#237;lico<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48-72 a&#241;os&#41;&#46; 46 &#40;6&#44;9&#37;&#41; pacientes presentaban unos niveles deficientes de vitamina D&#44; y 449 &#40;67&#44;7&#37;&#41; niveles insuficientes&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Quinientos sesenta y un pacientes &#40;84&#44;6&#37;&#41; presentaban un melanoma localizado &#40;estadios 0&#44; I y II&#41; y 102 &#40;15&#44;4&#37;&#41; ten&#237;an met&#225;stasis en el momento del diagn&#243;stico &#40;estadios III o IV&#41;&#46; Se objetivaron m&#225;s de 50 angiomas seniles en 26 pacientes &#40;4&#44;2&#37;&#41;&#44; y antecedentes personales de c&#225;ncer de piel no melanoma en 95 de los pacientes &#40;4&#44;4&#37;&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se detallan las caracter&#237;sticas de la poblaci&#243;n y las tablas de contingencia de los grupos de estudio&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Al analizar la distribuci&#243;n de las variables independientes estudiadas en los grupos definidos por la presencia o ausencia de un CPS no cut&#225;neo&#44; encontramos que el grupo que hab&#237;a desarrollado un CPS no cut&#225;neo ten&#237;a una proporci&#243;n significativamente mayor de pacientes mayores de 60 a&#241;os &#40;76&#44;5&#37; frente a 50&#44;4&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#41; y pacientes con 20 o menos nevos &#40;76&#44;5&#37; frente a 59&#44;5&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;049&#41;&#44; y una tendencia a presentar un melanoma nodular &#40;26&#44;5&#37; frente a 14&#44;9&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;071&#41; y un estadio avanzado &#40;III&#47;IV&#41; &#40;26&#44;5&#37; frente a 14&#44;8&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;066&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">No se encontraron diferencias estad&#237;sticamente significativas para las variables sexo&#44; niveles de vitamina D&#44; antecedentes personales de c&#225;ncer&#44; tipo histol&#243;gico&#44; antecedentes familiares de melanoma&#44; antecedentes familiares de c&#225;ncer&#44; exposici&#243;n solar&#44; angiomas seniles y antecedentes de carcinoma basocelular o epidermoide&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">An&#225;lisis de la incidencia acumulada</span><p id="par0110" class="elsevierStylePara elsevierViewall">Tras una mediana de seguimiento de 51&#44;3 meses&#44; 34 &#40;5&#44;1&#37;&#41; pacientes desarrollaron un CPS no cut&#225;neo&#46; La <a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> muestra que la incidencia esetimada global de CPS no cut&#225;neo a los cinco a&#241;os del 6&#44;1&#37;&#44; y a los diez a&#241;os&#44; del 8&#44;7&#37;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">En el an&#225;lisis estad&#237;stico univariante&#44; la incidencia acumulada estimada a 5 y 10 a&#241;os de CPS no cut&#225;neo fue del 9&#44;2&#37; para los pacientes con niveles deficientes de vitamina D&#44; del 6&#44;1&#37; y 8&#44;7&#37; para los pacientes con unos niveles insuficientes&#44; respectivamente&#44; y del 5&#44;4 y 8&#44;9&#37; en los pacientes con unos niveles suficientes&#44; respectivamente&#44; mostrando que los niveles de vitamina D no difer&#237;an significativamente en el tiempo de supervivencia para el desarrollo de un CPS no cut&#225;neo &#40;log-rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;817&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>a&#41;&#46; Entre las variables restantes&#44; se observaron diferencias significativas para la edad&#44; el n&#250;mero de nevos&#44; el melanoma nodular y el estadio III&#47;IV &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Los pacientes mayores de 60 a&#241;os tuvieron una incidencia significativamente mayor de un CPS no cut&#225;neo &#40;log rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En los pacientes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os&#44; la incidencia acumulada a los 5 y 10 a&#241;os fue del 9&#44;6&#37; y el 13&#44;9&#37;&#44; respectivamente&#46; Y del 2&#44;8&#37; y el 3&#44;9&#37; para los pacientes<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>b&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">En cuanto a la presencia de melanoma nodular &#40;log-rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;025&#41;&#44; la incidencia en los pacientes con un melanoma nodular fue del 8&#44;9&#37; a los cinco a&#241;os y del 14&#44;6&#37; a los diez a&#241;os&#44; mientras que los pacientes sin melanoma nodular tuvieron una incidencia acumulada a los 5 y 10 a&#241;os del 5&#44;6&#37; y el 7&#44;8&#37;&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>c&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Respecto al estadio &#40;log rank&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;025&#41;&#44; los pacientes con estadio III&#47;IV tuvieron una incidencia acumulada a los 5 y 10 a&#241;os del 11&#44;1&#37; y el 17&#44;9&#37;&#44; respectivamente&#46; Por el contrario&#44; los pacientes con estadio 0&#47;I&#47;II tuvieron una incidencia acumulada a los 5 a&#241;os del 5&#44;3&#37; y del 7&#44;5&#37; a los diez a&#241;os &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>d&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Tras el an&#225;lisis multivariable de riesgos proporcionales de Cox&#44; s&#243;lo la edad<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 a&#241;os &#40;HR 3&#44;4&#59; IC 95&#37; HR 1&#44;5-7&#44;6&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41; y el melanoma nodular &#40;HR 2&#44;2&#59; IC 95&#37; HR 1&#44;0-4&#44;8&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;038&#41; mantuvieron su asociaci&#243;n significativa con el desarrollo de un CPS no cut&#225;neo &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Discusi&#243;n</span><p id="par0140" class="elsevierStylePara elsevierViewall">Hemos realizado un estudio anal&#237;tico&#44; observacional&#44; longitudinal y retrospectivo basado en una cohorte de 663 pacientes diagnosticados de melanoma para evaluar la relaci&#243;n entre los niveles de vitamina D medidos en el momento del diagn&#243;stico y el desarrollo de una segunda neoplasia maligna no cut&#225;nea&#46; Los resultados han demostrado que la deficiencia de vitamina D en el momento del diagn&#243;stico de melanoma no aumenta el riesgo de desarrollar una segunda neoplasia maligna no cut&#225;nea&#46; Sin embargo&#44; analizando diferentes variables como el sexo&#44; la edad&#44; los antecedentes de melanoma y otras neoplasias&#44; hemos observado que presentar el melanoma a una edad superior a los 60 a&#241;os y el subtipo de melanoma nodular se asocian a un mayor riesgo de desarrollar segundas neoplasias malignas no cut&#225;neas&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Aunque algunos estudios hab&#237;an asociado previamente una menor edad en el momento del diagn&#243;stico del melanoma con un mayor riesgo de desarrollar segundos c&#225;nceres primarios<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a>&#44; numerosos estudios recientes han demostrado que una mayor edad aumenta el riesgo de m&#250;ltiples tumores primarios&#44; Adam C&#46; Krajewski et al&#46; realizaron un estudio prospectivo en 222 pacientes de edad &#62; o &#61; 65 a&#241;os diagnosticados de melanoma y observaron que&#44; tras una mediana de seguimiento de 5 a&#241;os&#44; alrededor del 10&#37; desarrollaron un segundo melanoma&#44; y el 4&#37; desarrollaron tres o m&#225;s melanomas&#44; lo que pone de manifiesto la importancia de un seguimiento estrecho en estos pacientes<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a>&#46; En nuestro estudio&#44; la edad superior a 60 a&#241;os se asoci&#243; de forma estad&#237;sticamente significativa con un aumento de otros tumores primarios no cut&#225;neos&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">La relaci&#243;n entre el envejecimiento y la incidencia de c&#225;ncer est&#225; bien establecida&#44; y el envejecimiento representa uno de los factores de riesgo m&#225;s cr&#237;ticos para el desarrollo de tumores&#46; Esta edad y el c&#225;ncer comparten algunos mecanismos biol&#243;gicos complejos&#44; como la inestabilidad gen&#243;mica con una acumulaci&#243;n progresiva de da&#241;o gen&#233;tico&#44; unas alteraciones epigen&#233;ticas &#40;debidas principalmente a la exposici&#243;n prolongada a carcin&#243;genos ambientales&#41; y un debilitamiento progresivo de los mecanismos de oncosupresi&#243;n vinculados a la inmunosenescencia<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">15&#44;16</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">La asociaci&#243;n entre el melanoma nodular y el riesgo de segundas neoplasias cut&#225;neas malignas es un hallazgo incidental e inesperado en nuestro estudio&#46; El melanoma nodular es&#44; por definici&#243;n histol&#243;gica&#44; un subtipo de melanoma que no muestra una fase de crecimiento radial y no muestra proliferaci&#243;n melanoc&#237;tica intrad&#233;rmica m&#225;s all&#225; de tres crestas epid&#233;rmicas en cada margen de la masa tumoral<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a>&#46; El melanoma nodular se ha asociado a un peor pron&#243;stico debido a un grosor de Breslow generalmente mayor en el momento del diagn&#243;stico&#46; Presenta procesos biol&#243;gicos intr&#237;nsecamente m&#225;s agresivos que el melanoma de extensi&#243;n superficial<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Desde un punto de vista molecular&#44; el melanoma nodular muestra una mayor frecuencia de mutaci&#243;n en <span class="elsevierStyleItalic">NRAS</span> que el melanoma de extensi&#243;n superficial&#44; aunque no se han demostrado diferencias en la tasa de mutaci&#243;n <span class="elsevierStyleItalic">BRAF</span> en este subtipo de melanoma&#46; Adem&#225;s&#44; el MN parece mostrar una menor prevalencia de genes som&#225;ticos mutados que el MES<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; El melanoma nodular tambi&#233;n muestra una mayor frecuencia de mutaciones en el promotor de <span class="elsevierStyleItalic">TERT</span> que otros subtipos<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">19&#44;20</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Dado que los pacientes con un melanoma nodular tienen una tasa de mortalidad m&#225;s elevada&#44; cabr&#237;a esperar que el riesgo de segundas neoplasias malignas se redujera en este subgrupo de pacientes debido a la menor tasa de supervivencia&#46; Sin embargo&#44; en un estudio de 2022&#44; Yen T&#46; Luu et al&#46;&#44; utilizando la base de datos Surveillance&#44; Epidemiology&#44; and End Results &#40;SEER&#41;&#44; demostraron que los supervivientes de MN&#44; en comparaci&#243;n con otros histotipos&#44; ten&#237;an un riesgo un 27&#37; mayor de desarrollar segundas neoplasias malignas primarias<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a>&#46; Este resultado parece coincidir con el nuestro&#44; pero actualmente faltan m&#225;s datos de apoyo en la literatura&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Las posibles causas son muchas y a&#250;n est&#225;n por dilucidar&#46; La susceptibilidad gen&#233;tica individual puede desempe&#241;ar un papel importante en la predisposici&#243;n a estos tumores&#44; al igual que los factores de riesgo ambientales o inmunol&#243;gicos&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Adem&#225;s&#44; los pacientes con MN tienden a tener tumores m&#225;s gruesos y&#44; por tanto&#44; una mayor tasa de tratamiento que los pacientes con otros tipos de melanoma&#46; No se puede excluir que la terapia pueda desempe&#241;ar un papel importante en el desarrollo de un CPS&#59; sin embargo&#44; en este estudio no se recogieron datos sobre la terapia de los pacientes&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Algunas limitaciones y puntos fuertes del presente estudio merecen consideraci&#243;n&#46; En primer lugar&#44; nuestro estudio incluye datos de un &#250;nico centro&#44; por lo que la poblaci&#243;n estudiada puede no representar a la poblaci&#243;n general&#46; Adem&#225;s&#44; la muestra analizada es num&#233;ricamente limitada&#44; ya que considera 663 pacientes&#44; de los cuales s&#243;lo 34 desarrollaron una segunda neoplasia primaria&#46; En segundo lugar&#44; dado que los valores de vitamina D se recogieron durante un periodo relativamente corto&#44; el tiempo de seguimiento de los pacientes tambi&#233;n es limitado &#40;51&#44;3 meses de media&#41;&#46; En cuanto a los niveles de vitamina D&#44; se utilizaron los rangos establecidos para el metabolismo &#243;seo&#44; pero &#233;stos podr&#237;an variar en funci&#243;n del desarrollo tumoral&#46; No se realiz&#243; un an&#225;lisis del punto de corte de vitamina D&#46; Otra limitaci&#243;n de nuestro estudio es la falta de caracterizaci&#243;n del tipo de neoplasias primarias secundarias desarrolladas por los pacientes&#46; Por &#250;ltimo&#44; en cuanto a la correlaci&#243;n entre un CPS no cut&#225;neo y el melanoma nodular&#44; al tratarse de un hallazgo incidental e inesperado&#44; no tuvimos en cuenta otras variables&#44; como las caracter&#237;sticas moleculares&#44; el sustrato gen&#233;tico y las terapias actuales de estos pacientes&#44; que podr&#237;an aportar informaci&#243;n importante y que representan hasta la fecha un campo inexplorado digno de mayor estudio&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Por otro lado&#44; el hecho de que los datos se obtuvieran prospectivamente de un &#250;nico centro&#44; con valores analizados por el mismo laboratorio&#44; hizo posible la obtenci&#243;n de una colecci&#243;n de datos homog&#233;nea&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">En conclusi&#243;n&#44; seg&#250;n nuestro estudio&#44; la deficiencia de vitamina D no se asocia a un mayor riesgo de desarrollar un CPS no cut&#225;neo en pacientes con melanoma&#46; Al mismo tiempo&#44; la edad superior a 60 a&#241;os y el melanoma nodular parecen tener un valor predictivo positivo para desarrollar un CPS no cut&#225;neo&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Se necesitan m&#225;s estudios para caracterizar la relaci&#243;n entre el MN y el CPS no cut&#225;neo y para comprender los complejos mecanismos biol&#243;gicos subyacentes&#46; No obstante&#44; nuestros datos confirman la importancia de un seguimiento estrecho de estos pacientes&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicto de intereses</span><p id="par0200" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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              "titulo" => "An&#225;lisis de la incidencia acumulada"
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            1 => "Melanoma"
            2 => "Segundos canceres primarios"
            3 => "Melanoma nodular"
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            1 => "Melanoma"
            2 => "Second primary cancer"
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    "resumen" => array:2 [
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Antecedentes</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El d&#233;ficit de vitamina D se asocia con un mayor riesgo de padecer varias enfermedades&#44; incluido el c&#225;ncer&#46; Molecularmente&#44; esta parece tener un efecto antineopl&#225;sico&#46; Sin embargo&#44; el papel que juega en la patog&#233;nesis del c&#225;ncer no est&#225; bien esclarecido y hay resultados dispares en los estudios publicados&#46; El objetivo del presente fue determinar si unos niveles de vitamina D deficientes en el momento del diagn&#243;stico del melanoma aumentaba el riesgo de desarrollar un c&#225;ncer no cut&#225;neo &#40;CNC&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material y m&#233;todo</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Se dise&#241;&#243; un estudio retrospectivo de 663 pacientes diagnosticados de melanoma entre el 1 de enero de 2011 y el 31 de octubre de 2022&#46; El efecto de cada una de las variables seleccionadas en el desarrollo de un CNC durante el seguimiento tras el diagn&#243;stico del melanoma se realiz&#243; mediante el estudio de supervivencia con el m&#233;todo de Kaplan-Meier y las diferencias se evaluaron con la prueba de los rangos logar&#237;tmicos&#46; Se elaboraron modelos uni y multivariados de riesgos proporcionales de Cox para cuantificar el efecto de cada valor de las variables de estudio en el tiempo para desarrollar un CNC&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">De los 663 pacientes&#44; 34 desarrollaron un CNC tras el melanoma&#46; No hubo diferencias estad&#237;sticamente significativas entre los grupos definidos por los niveles de vitamina D &#40;<span class="elsevierStyleItalic">log-rank</span>&#44; p &#61; 0&#44;761&#41;&#46; Sin embargo&#44; una edad &#62; 60&#44; el estadio III&#47;IV&#44; y el tipo nodular se asociaron significativamente al desarrollo de un CNC&#46; Tras el an&#225;lisis multivariado&#44; solo la edad &#62; 60 &#40;<span class="elsevierStyleItalic">hazard ratio</span> &#91;HR&#93; 3&#44;4&#59; intervalo de confianza &#91;IC&#93; 95&#37; HR&#58;1&#44;5-7&#44;6&#41; y el subtipo nodular de melanoma &#40;HR 2&#44;2&#59; IC 95&#37; HR&#58;1&#44;0-4&#44;8&#41; se mantuvieron en el modelo predictivo final&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Nuestros resultados sugieren que unos niveles de vitamina D deficientes en el diagn&#243;stico de melanoma no se asocian a un mayor riesgo de desarrollar un CNC&#46; Sin embargo&#44; en una edad &#62; 60 y el subtipo nodular s&#237; que aumentan el riesgo de desarrollar un CNC&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Background</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Vitamin D deficiency associates with the risk of developing many diseases&#44; including cancer&#46; At the molecular level&#44; vitamin D appears to have an antineoplastic effect&#46; However&#44; the role of vitamin D deficiency in cancer pathogenesis remains unelucidated and numerous studies have resulted in discordant results&#46; This study aimed to determine whether vitamin D deficiency during melanoma diagnosis increases the risk of developing non-cutaneous second primary cancers &#40;SPC&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Materials and methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A retrospective study on 663 patients diagnosed with melanoma between 1 January 2011 and 31 October 2022&#46; The effect of each variable on the development of a subsequent non-cutaneous cancer was performed using Kaplan&#8211;Meier curves and differences were assessed by log-rank tests&#46; Cox proportional hazard univariate and multivariate models were used to quantify the effect of each variable in the time to develop a non-cutaneous neoplasia&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Out of 663 patients&#44; 34 developed a non-cutaneous SPC&#46; There was no statistically significant association between vitamin D levels and non-cutaneous SPC development &#40;log-rank&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;761&#41;&#46; Age<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 years&#44; stage III&#47;IV&#44; and nodular melanoma subtype were significantly associated with the development of a SPC&#46; After multivariate analysis&#44; only age<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>60 years &#40;HR 3&#46;4&#59; HR CI 95&#37;&#58; 1&#46;5&#8211;7&#46;6&#41; and nodular melanoma subtype &#40;HR 2&#46;2&#59; HR CI 95&#37;&#58; 1&#46;0&#8211;4&#46;8&#41; were included in the final model&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Our results suggest that vitamin D deficiency is not associated with an increased risk of developing non-cutaneous SPC in melanoma patients&#46; However&#44; age over 60 years and nodular melanoma subtype increase the risk for non-cutaneous SPC development&#46;</p></span>"
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          "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Curva de Kaplan-Meier que representa la incidencia acumulada global de CPS no cut&#225;neo en pacientes con melanoma&#46;</p>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">No</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col">Si</th><th class="td" title="\n
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                  \t\t\t\t\ttable-head\n
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                  \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"><span class="elsevierStyleItalic">N</span>&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">&#37;&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"><span class="elsevierStyleItalic">N</span>&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">&#37;&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&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
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">320&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">312&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">49&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">343&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">317&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hombre&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">361&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;374</span>&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"><span class="elsevierStyleHsp" style=""></span>Mujer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">302&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">284&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">52&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Niveles de Vitamina D &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Deficiente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">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">6&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;761</span>&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Insuficiente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">449&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">425&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">70&#44;6&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\ttop\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">168&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes personales de c&#225;ncer &#40;v&#46;p</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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\ttop\n
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                  \t\t\t\t">594&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#44;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">565&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">89&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">85&#44;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Tipos histol&#243;gicos &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>LMM&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">132&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">19&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">124&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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#44;5&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\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MES&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">354&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">341&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">54&#44;3&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">13&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>MN&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
                  \t\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">15&#44;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">94&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">14&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&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"><span class="elsevierStyleHsp" style=""></span>MA&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&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"><span class="elsevierStyleHsp" style=""></span>Otros&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;8&nbsp;\t\t\t\t\t\t\n
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                  \t\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Melanoma Nodular &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\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">560&nbsp;\t\t\t\t\t\t\n
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                  \t\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&#44;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">535&nbsp;\t\t\t\t\t\t\n
                  \t\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">85&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;071</span>&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"><span class="elsevierStyleHsp" style=""></span>Si&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes familiares de melanoma &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">6&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">593&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&#44;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">560&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;170</span>&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"><span class="elsevierStyleHsp" style=""></span>Si&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#44;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Antecedentes familiares de c&#225;ncer &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">307&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;292</span>&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"><span class="elsevierStyleHsp" style=""></span>Si&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">346&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53&#44;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">325&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">N&#250;mero de nevus &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">22&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>&#60;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">387&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">361&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">76&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;049</span>&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"><span class="elsevierStyleHsp" style=""></span>&#8805;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">254&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#44;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">246&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="8" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Exposici&#243;n al sol &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">18&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>&#8804;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">573&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">543&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Estadio de la enfermedad &#40;v&#46;p&#46;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">0&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Incidencia acumulada a los 10 a&#241;os&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" scope="col" style="border-bottom: 2px solid black">Log rank&#44; <span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&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">9&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">9&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#44;4&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;60&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  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 00017310
Original language: Spanish
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