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Are HCTZ-Containing Products Associated With Increased Risk of Non-Melanoma Skin Cancers?

By: Noelle Cutter, PhD
Posted: Wednesday, April 7, 2021

Recent studies have found an elevated risk of non-melanoma skin cancer associated with hydrochlorothiazide (HCTZ)-containing products due to its photosensitizing properties. Efe Eworuke, PhD, and colleagues at the Center for Drug Evaluation and Research, U.S. Food and Drug Administration, determined that among White individuals, there appears to be a “small” increased risk of both basal cell and squamous cell carcinomas with the use of HCTZ compared with angiotensin-converting enzyme (ACE) inhibitors. The results of their study were published in JNCI Cancer Spectrum

This retrospective study focused on more than five million patients to compare the exposure of taking HCTZ-containing products with patients who received ACE inhibitors alone or in combination with non-HCTZ products. Cumulative and individual hazard ratios (HRs) were calculated using Cox proportional hazards regression model. Incidence rate ratios (IRRs) were adjusted for site and age by cumulative HCTZ dose.

Results indicated the incidence rate of basal cell carcinoma was higher than that of squamous cell carcinoma in both exposure cohorts: 2.78 and 1.66 for HCTZ, 2.82 and 1.60 for ACEI, respectively. There appeared to be an increased risk for squamous cell carcinoma (HR = 1.04, 95% confidence interval [CI] = 1.02–1.06) but no difference in overall risk between HCTZ and ACE inhibitors for basal cell carcinoma (HR = 0.99, 95% CI = 0.97–1.00). Among White individuals, HCTZ use was correlated with higher risks for both squamous cell carcinoma (HR = 1.15, 95% CI = 1.12–1.17) and basal cell carcinoma (HR = 1.09, 95% CI = 1.05–1.35). In the overall population, an increased risk of squamous cell carcinoma was seen with cumulative HCTZ doses ≥ 50,000 mg (IRR = 1.19, 95% CI = 1.05–1.35); and the association seemed to be stronger in White individuals (IRR = 1.27, 95% CI = 1.10–1.47).

“Patients should take risk-mitigating steps including protection from prolonged sun exposure and following up clinically on any skin lesions while using HCTZ-containing products longer term,” the authors recommended.

Disclosure: The authors reported no conflicts of interest.



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