Association Between the Use of Thiazide Diuretics and the Risk of Skin Cancers: A Meta-Analysis of Observational Studies

BACKGROUND: Thiazide diuretics are among the most widely prescribed antihypertensive agents. Given their photosensitizing effects, however, there are concerns that they may increase the risk of skin cancers. In this meta-analysis, we investigated an association between the use of thiazide diuretics and the risk of skin cancers. METHODS: We identified studies by searching three electronic databases (PubMed, EMBASE, and the Cochrane Library) from their inception to October 30, 2017. Nine relevant observational studies (seven case-control and two cohort studies) were included in this study. Since included studies were unlikely to be functionally equal, pooled estimates were calculated using random-effects meta-analysis. RESULTS: The use of thiazide diuretics was associated with an increased risk of squamous cell carcinoma (adjusted odds ratio (aOR), 1.86; 95% confidence interval (CI), 1.23 - 2.80) and marginally increased risk of basal cell carcinoma (aOR, 1.19; 95% CI, 1.02 - 1.38) and malignant melanoma (aOR, 1.14; 95% CI, 1.01 - 1.29). In the subgroup analysis, hydrochlorothiazide or hydrochlorothiazide combination medications were significantly associated with squamous cell carcinoma without significant heterogeneity among studies (aOR, 2.04; 95% CI, 1.79 - 2.33; Higgin’s I(2) value = 0.0 %; Q-statistics = 2.7, P value = 0.445). CONCLUSIONS: Our results suggested that the use of thiazide diuretics may be associated with an increased risk of skin cancers. This association was most prominent between the use of hydrochlorothiazide or hydrochlorothiazide combination medications and the risk of squamous cell carcinoma. Further studies are needed to confirm these findings.