Hydrochlorothiazide use and the risk of skin cancer in patients with hypertensive disorder: a nationwide retrospective cohort study from Korea

Background/Aims Recent studies have shown a cumulative dose-dependent association between the use of hydrochlorothiazide (HCTZ) and skin cancer, including melanoma and non-melanoma skin cancer (NMSC) in Western Europe. However, whether this pattern is present in East Asia countries is unknown. The aim of this study was to examine the association between HCTZ use and the risk of skin cancer among a cohort of hypertensive patients in South Korea. Methods This was a retrospective, population-based cohort study using the database from the Health Insurance Review and Assessment Service between January 1, 2007 and June 30, 2017 in South Korea. We identified patients diagnosed with melanoma and NMSC in the cohorts of essential hypertensive patients who were treated with HCTZ or antihypertensive agents other than HCTZ. Using Cox proportional hazards regression models, the hazard ratios (HR) for skin cancer associated with HCTZ users were calculated. Results The risk of melanoma was significantly lower in HCTZ-users compared with non-HCTZ users (HR, 0.85; 95% confidence interval [CI], 0.75 to 0.97; p = 0.016), and the risk of NMSC was lower in the HCTZ users but no statistically significant association was seen (HR, 0.96; 95% CI, 0.91 to 1.02; p = 0.236). High cumulative doses (≥ 50,000 mg) of HCTZ were associated with decreased risk of both NMSC (HR, 0.20; 95% CI, 0.10 to 0.38; p < 0.001) and melanoma (HR, 0.18; 95% CI, 0.04 to 0.70; p = 0.001), respectively. Conclusions High cumulative use of HCTZ may have a chemopreventive effect against the development of melanoma and NMSC with clear cumulative dose-response and duration-response relationships in South Korea