Use of Hydrochlorothiazide and Risk of Melanoma and Nonmelanoma Skin Cancer

Introduction: There are concerns that hydrochlorothiazide may increase the risk of incident nonmelanoma (cutaneous squamous cell carcinoma [cSCC], basal cell carcinoma [BCC]) and melanoma skin cancer, with regulatory agencies and societies calling for additional studies.

Methods: We conducted a propensity score-matched population-based cohort study using the United Kingdom Clinical Practice Research Datalink. A total of 20,513 new users of hydrochlorothiazide were propensity score matched, in a 1:1 ratio, to new users of other thiazide diuretics between January 1, 1988 and March 31, 2018, with follow-up until March 31, 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for cSCC, BCC, and melanoma, comparing use of hydrochlorothiazide with use of other thiazide diuretics overall, by cumulative duration of use, and cumulative dose.

Results: After an 8.6-year median follow-up, hydrochlorothiazide was associated with an increased risk of cSCC (HR 1.50, 95% CI 1.06-2.11). HRs increased with cumulative duration of use, with evidence of an association after 5-10 years (HR 2.10, 95% CI 1.20-3.67) and highest after > 10 years (HR 3.70, 95% CI 1.77-7.73). Similarly, HRs increased with cumulative dose, with higher estimates for ≥ 100,000 mg (HR 4.96, 95% CI 2.51-9.81). In contrast, hydrochlorothiazide was not associated with an increased risk of BCC (HR 1.01, 95% CI 0.91-1.13) or melanoma (HR 0.82, 95% CI 0.63-1.08), with no evidence of duration- or dose-response relationships.

Conclusions: Use of hydrochlorothiazide was associated with an increased risk of cSCC and with evidence of a duration- and dose-response relationship. In contrast, no association was observed for BCC or melanoma.