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

J Am Acad Dermatol. 2019 Feb;80(2):460-465.e9. doi: 10.1016/j.jaad.2018.06.014. Epub 2018 Jun 18.

Abstract

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.

Keywords: Merkel cell carcinoma; antihypertensives; epidemiology; hydrochlorothiazide; malignant adnexal skin tumors; pharmacology; skin cancer.

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Carcinoma, Merkel Cell / chemically induced*
  • Carcinoma, Merkel Cell / epidemiology
  • Carcinoma, Merkel Cell / pathology
  • Case-Control Studies
  • Denmark
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hydrochlorothiazide / adverse effects*
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / diagnosis
  • Hypertension / drug therapy
  • Incidence
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Adnexal and Skin Appendage / chemically induced*
  • Neoplasms, Adnexal and Skin Appendage / epidemiology
  • Neoplasms, Adnexal and Skin Appendage / pathology
  • Odds Ratio
  • Prognosis
  • Registries*
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / pathology
  • Survival Analysis

Substances

  • Hydrochlorothiazide