Use of Thiazide Diuretics and Risk of All Types of Skin Cancers: An Updated Systematic Review and Meta-Analysis

Abstract

Background: The use of thiazide diuretics is associated with skin cancer risk; however, whether this applies to all skin cancer types is unclear. Methods: In this meta-analysis, we searched multiple electronic databases and gray literature up to 10 April 2022, with no language restrictions, to identify relevant randomized controlled trials (RCTs) and non-randomized studies (cohort, case-control) that investigated the association between thiazide diuretics and skin cancer. The primary outcomes of interest were malignant melanoma and non-melanoma skin cancer (basal cell carcinoma [BCC], squamous cell carcinoma [SCC]). Secondary outcomes included other skin cancers (lip cancer, Merkel cell carcinoma, malignant adnexal skin tumors, oral cavity cancer, and precursors of skin cancer). We used a random-effects meta-analysis to estimate pooled adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirty non-randomized studies (17 case-control, 13 cohort, no RCTs) were included. Thiazide diuretic users had a higher risk of malignant melanoma (17 studies; n = 10,129,196; pooled adjusted OR, 1.10; 95% CI, 1.04–1.15; p < 0.001; strength of evidence, very low; very small harmful effect), BCC (14 studies; n = 19,780,476; pooled adjusted OR, 1.05; 95% CI, 1.02–1.09; p = 0.003; strength of evidence, very low; very small harmful effect), and SCC (16 studies; n = 16,387,862; pooled adjusted OR, 1.35; 95% CI, 1.22–1.48; p < 0.001; strength of evidence, very low; very small harmful effect) than non-users. Thiazide diuretic use was also associated with a higher risk of lip cancer (5 studies; n = 161,491; pooled adjusted OR, 1.92; 95% CI, 1.52–2.42; p < 0.001; strength of evidence, very low; small harmful effect), whereas other secondary outcomes were inconclusive. Conclusions: Thiazide diuretics are associated with the risk of all skin cancer types, including malignant melanoma; thus, they should be used with caution in clinical practice.

Association Between Pretransplant Dialysis Modality and Kidney Transplant Outcomes

“…using the Cochrane risk-of-bias tool for randomized trials and the Newcastle-Ottawa Scale (NOS; score range: 0-9, with the higher scores indicating the higher quality of the study) for nonrandomized studies . The overall risk of bias was then categorized as low, high, or of some concern for randomized trials and the highest quality (NOS score ≥8 points) for nonrandomized studies . Any discrepancies in each review step were resolved through consensus discussion.…”

“…16 The overall risk of bias was then categorized as low, high, or of some concern for randomized trials and the highest quality (NOS score Ն8 points) for nonrandomized studies. 17,18 Any discrepancies in each review step were resolved through consensus discussion.…”

“…16 The overall risk of bias was then categorized as low, high, or of some concern for randomized trials and the highest quality (NOS score Ն8 points) for nonrandomized studies. 17,18 Any discrepancies in each review step were resolved through consensus discussion. methodological and statistical heterogeneity between studies, a random-effects model was used to estimate the pooled adjusted hazard ratio (HR) or odds ratio with a corresponding 95% CI as common risk estimates across the included studies.…”

Does systemic hydrochlorothiazide increase the risk of developing ultraviolet radiation‐induced skin tumours in hairless mice?

“…8 Whether HCTZ affects the skin in the same way remains unclear, because various studies have produced conflicting results. [6][7][8][9][10][11][12][13][14][15][16][17] HCTZ is currently being assessed for potentially co-carcinogenic effects in ultraviolet radiation (UVR)-induced skin cancer. [6][7][8][9][10][11][12][13][14][15][16] Previously, a significant dose-response relationship between HCTZ use and an elevated risk of SCC has been shown.…”

“…6,[9][10][11][12][13] A meta-analysis found an association between using thiazide diuretics and an increased risk of all types of skin cancer, including MM. 17 Other studies have shown that HCTZ has little or no effect on the risk of developing BCC. 6,12 Jensen et al suggested that sun-protective measures alone may be insufficient to counteract the carcinogenic potential of HCTZ.…”