Original articleHydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study
Section snippets
Methods
We performed a nested case-control study, similarly to our recent studies,4, 5, 6 on the basis of the nationwide Danish demographic and health registries (Supplementary Appendix; available at http://www.jaad.org).
From the Danish Cancer Registry,16 we identified patients (cases) with a histologically verified primary diagnosis of Merkel cell carcinoma or malignant adnexal skin tumor during January 1, 2004-December 31, 2015 (study period). Supplemental Table I (available at http://www.jaad.org)
Results
We included 97 patients with Merkel cell carcinoma and 132 with malignant adnexal skin tumors (Fig 1) matched to 1857 and 2620 population controls, respectively. Baseline characteristics were similar between patients with malignant adnexal skin tumors and controls (Table I); however, Merkel cell carcinoma patients had higher numbers of comorbidities and drug use, in particular of the photosensitizing drugs macrolides and aminoquinolines, and had a higher level of education compared with their
Discussion
In this large nationwide population-based study, we found a 2.3-fold increased risk for Merkel cell carcinoma and a 3.6-fold increased risk for malignant adnexal skin tumors associated with high use of hydrochlorothiazide.
Epidemiologic studies of risk factors of these rare skin tumors are scarce. The use of nationwide Danish registries enabled the identification of cases and controls with low risk for selection bias. Case diagnoses were histologically verified, further enhancing validity. We
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Cited by (40)
What Dermatologists Should Know About Thiazides
2022, Actas Dermo-Sifiliograficas[Translated article] What Dermatologists Should Know About Thiazides
2022, Actas Dermo-SifiliograficasDiagnosis and treatment of arterial hypertension 2021
2022, Kidney InternationalCitation Excerpt :In the past decades, repeatedly, potential side effects of antihypertensive medication regarding cancer were assumed, which however could not be confirmed afterward.62 Very recently, several observational studies highlighted an increased risk of several types of skin cancer with the use of thiazide diuretics.63–66 Although there is no evidence to suggest that thiazide diuretics and in particular HCT per se are causing skin cancer, its photosensitizing properties may enhance the detrimental effects of sun exposure, and potentially the risk of developing several skin cancers.
Reply to “Comment on ‘Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case–control study from Denmark’”
2021, Journal of the American Academy of Dermatology
Funding sources: Supported by a grant from the Danish Cancer Society (grant R72-A4417) and the Danish Council of Independent Research (grant 4004-00234B). The funding source had no role in the design of the study, data analysis, or interpretation of the results.
Conflicts of interest: Dr Gaist received honoraria from AstraZeneca (Sweden) for participating as a coinvestigator in a research project outside this work. Dr Pottegård has participated in research projects unrelated to the present study using grants provided by LEO Pharma (manufacturer of bendroflumethiazide) to the institution where he was employed. The remaining authors disclose no relevant conflicts of interest.