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Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study

      Background

      Hydrochlorothiazide use has been associated with markedly increased risk for squamous cell carcinoma. No previous studies have investigated the association between hydrochlorothiazide use and the risk for Merkel cell carcinoma (MCC) and malignant adnexal skin tumors (MAST).

      Objective

      To examine the association between hydrochlorothiazide use and the risk for MCC and MAST.

      Methods

      Using Danish nationwide health registries, we identified all patients with incident MCC or MAST during 2004-2015 and matched the cases individually to cancer-free population controls by risk set sampling. Using conditional logistic regression, we estimated the odds ratios (ORs) and confidence intervals (CIs) associated with cumulative use of hydrochlorothiazide.

      Results

      The adjusted ORs for MCC and MAST associated with high use (≥50,000 mg) of hydrochlorothiazide was 2.3 (95% CI 1.1-4.8) and 3.6 (95% CI 1.9-7.0), respectively, which increased to 3.3 (95% CI 1.3-8.3) and 5.6 (95% CI 2.4-13.3), respectively, with highest use (≥100,000 mg). We found no increased risk for these tumors in analyses of drugs with similar indications as hydrochlorothiazide, except there was a tendency toward an increased risk for MCC associated with the use of furosemide (OR 1.9, 95% CI 0.9-4.0).

      Limitations

      No data on sun exposure was available.

      Conclusion

      Hydrochlorothiazide use is associated with an increased risk for MCC and MAST.

      Key words

      Abbreviations used:

      CI (confidence interval), OR (odds ratio), UV (ultraviolet)
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      Linked Article

      • Thiazides and nonmelanoma skin cancer: Is it a class effect?
        Journal of the American Academy of DermatologyVol. 82Issue 1
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          To the Editor: We read with interest the article by Pedersen et al,1 who studied the association between hydrochlorothiazide (HTZ) use and the risk of nonmelanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). To further assess this association and to study NMSC as a possible thiazide class effect, we searched in VigiBase, the World Health Organization's pharmacovigilance database, for thiazide-associated reports associated with the preferred terms BCC and SCC from the Medical Dictionary for Regulatory Activities from January 1, 2004, to December 31, 2012.
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