HCTZ-Linked Skin Cancer Risk Observed Primarily in White Patients: Study

A new research published in the journal of Environmental Toxicology and Pharmacology revealed that hydrochlorothiazide (HCTZ) use was associated with an increased risk of skin cancers among white patients, while similar associations were not seen in other racial groups. These findings may help guide thiazide diuretic prescribing decisions in this population.

HCTZ is one of the widely prescribed antihypertensive medications and previous studies have linked this drug to photosensitivity to ultraviolet (UV) radiation and may contribute to cancer development. However, most earlier research focused heavily on predominantly White populations, leaving uncertainty about whether the risk extended equally across racial groups.

The study focused on adults newly treated for hypertension and compared patients taking HCTZ and other thiazide diuretics with those prescribed non-diuretic antihypertensive drugs (NDAHs). TriNetX global health research network was used to examine whether skin cancer risks associated with thiazide diuretics differ across racial groups. This study applied propensity score matching to account for baseline health differences and calculated adjusted hazard ratios (aHRs) for multiple skin cancers.

The findings showed a significant increase in skin cancer risk among White patients taking HCTZ. When compared to NDAH users, White patients on HCTZ experienced a 40% higher risk of keratinocyte carcinomas (KC), a 75% higher risk of squamous cell carcinoma (SCC), a 46% higher risk of basal cell carcinoma (BCC), and a 37% higher risk of malignant melanoma.

In contrast, this research found no statistically significant increase in skin cancer risk among Asian, Hispanic, or Black patients using HCTZ. The study also evaluated chlorthalidone, another thiazide diuretic, and observed a similar racial pattern, with elevated keratinocyte carcinoma rates appearing only in White individuals.

Overall, these findings highlight the importance of considering race and skin cancer susceptibility when prescribing thiazide diuretics. While the study does not suggest that patients should abruptly stop taking HCTZ, it may encourage clinicians to weigh individual risk factors, particularly in White patients with high sun exposure. Additional studies are required to better understand the biological and environmental reasons behind the racial differences observed in this study.

Reference:

Lee, C.-N., Shao, S.-C., Yang, C.-C., Hung, J.-H., Lai, E. C.-C., & Chi, C.-C. (2026). Risk of skin cancer from hydrochlorothiazide and other diuretics across races: a global cohort study. Environmental Toxicology and Pharmacology, 105043, 105043. https://doi.org/10.1016/j.etap.2026.105043