(285) Associations of Thiazide Use with Skin Cancers: A Systematic Review and Meta-Analysis

Publication Number: 616

Background: Among first-line antihypertensives, thiazide diuretics have photosensitizing properties with a biologically plausible causal association with skin cancers. However, previous findings on the associations of thiazide use with skin cancers were conflicting.

Objectives: To examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.

Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Nonmelanoma skin cancer (NMSC) and melanoma were analyzed separately. A random-effects model meta-analysis was conducted to measure the odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use.

Results: We included 14, 5, and 5 observational studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,837,748 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.17, 95% CI 1.08-1.26; HR 1.26, 95% CI 1.04-1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06-1.65; HR 1.61, 95% CI 0.97-2.67), and melanoma (OR 1.11, 95% CI 1.02-1.20; Asian countries: OR 0.90, 95% CI 0.82-0.99; non-Asian countries: OR 1.14, 95% CI 1.10-1.19). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43-4.57; HR 1.20, 95% CI 1.00-1.45) Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05-1.33), nodular (OR 1.23, 95% CI 1.08-1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08-1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide.

Conclusions: Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions.