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

Abstract

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.

Association between Use of Hydrochlorothiazide and Nonmelanoma Skin Cancer: Common Data Model Cohort Study in Asian Population

“…Recently, a few studies were also conducted to clarify this association in Asia. From a nationwide cohort study conducted in South Korea, the protective effect of HCTZ has not observed the development of melanoma and non-melanoma skin cancer [ 27 ]. However, from another nationwide cohort study conducted in Taiwan, Pottegård et al have reached limited evidence of HCTZ use associated with an increased risk of skin cancer [ 19 ].…”

Use of hydrochlorothiazide and risk of nonmelanoma skin cancer in Koreans: a retrospective cohort study using administrative healthcare data

“…Although two recent East Asian studies showed no significant association between HCTZ use and risk of NMSC, 11,12 one was a case-control study with a short follow-up period 11 and the other had potential selection bias because only patients with hypertension were included. 12 Thus, we performed a long-term retrospective cohort study of Korean participants using a nationwide sample cohort to investigate the risk of NMSC in relation to use of HCTZ and the effect of age on the outcome.…”

Response to comment on “Hydrochlorothiazide use and the risk of skin cancer in patients with hypertensive disorder: a nationwide retrospective cohort study from Korea”

“…We thank Drs. Pottegard and Morales for their thoughtful comments on our article entitled "Hydrochlorothiazide use and the risk of skin cancer in patients with hypertensive disorder: a nationwide retrospective cohort study from Korea" [1].…”