Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study

Background: The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. Objective: To determine whether HCTZ is associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors and calcium channel blockers.Methods: Two new-user, active comparator cohorts were assembled using 6 Canadian databases. Site -specific hazard ratios (HRs) with 95% CIs were estimated using standardized morbidity ratio weighted Cox proportional hazard models and pooled using random-effects meta-analysis.Results: HCTZ was not associated with an overall increased risk of keratinocyte carcinoma compared with angiotensin-converting enzyme inhibitors or calcium channel blockers, although increased risks were observed with longer durations (& GE;10 years; HR: 1.12; 95% CI: 1.03-1.21) and higher cumulative doses (& GE;100,000 mg; HR: 1.49; 95% CI: 1.27-1.76). For melanoma, there was no association with angiotensin-converting enzyme inhibitors, but a 32% increased risk with calcium channel blockers (crude incidence rates: 64.2 vs 58.4 per 100,000 person-years; HR: 1.32; 95% CI: 1.19-1.46; estimated number needed to harm at 5 years of follow-up: 1627 patients), with increased risks with longer durations and cumulative doses. Limitations: Residual confounding due to the observational design.Conclusions: Increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ. ( J Am Acad Dermatol 2023;89:243-53.)