Impact of Hydrochlorothiazide on Nonmelanoma Skin Cancer: A Distributed Network Analysis of 11 Real-world Databases

Hydrochlorothiazide (HCTZ) has carcinogenic effects owing to its photosensitizing properties. Recent studies have reported inconsistent results regarding the association between HCTZ and skin cancer.

This study aimed to clarify the effects of HCTZ on the risk of developing nonmelanoma skin cancer (NMSC) in Korean patients with hypertension.

This multicenter, retrospective cohort study was conducted using clinical data from 11 hospitals in Korea, and converted to the Observational Medical Outcomes Partnership-Common Data Model. Large-scale 1:1 propensity score-matching was conducted to balance the target and comparator cohorts. Cox regression analysis was used to examine the hazard ratio (HR) for NMSC in HCTZ users compared to HCTZ never-users.

8,821 patients and same number of controls were pooled from 11 databases. HCTZ use was not associated with a decreased risk of NMSC (HR, 1.01; 95% confidence interval [CI], 0.70-1.47). In the dose-response analysis, no significant correlation was found between NMSC risk and HCTZ dose for <1 year (HR, 1.17; 95% CI, 0.64-2.17) and ≥1 year (HR, 1.02; 95% CI, 0.64-1.61). No significant increase in the risk of NMSC was observed in the subgroup analyses for either age or sex.

HCTZ was not associated with the development of NMSC in a Korean hypertensive population, regardless of the duration of drug exposure.