THIAZIDE AND THIAZIDE-LIKE DIURETICS AS PHOTOSENSITIZERS AND THE RISK OF SKIN CANCER

Abstract

Objective: Thiazide diuretics and particularly hydrochlorothiazide were recently linked to an increased risk of skin cancer, which was attributed to the photosensitizing properties of these drugs. Given the widespread use of thiazide diuretics, a potential skin cancer promoting effect would impose an important public health concern. Thus, the objective of our review was to critically appraise the association between the use of thiazide and thiazide-like diuretics and the risk of skin cancer. Design and method: We evaluated the chemical structures and the photosensitizing potential of selected thiazide and thiazide-like diuretics. Moreover, we searched Pubmed from inception up to December 2018 for observational studies assessing the association between the use of thiazide or thiazide-like diuretics and the risk of any type of skin cancer. Finally, we assessed the quality of the studies for major methodological biases. Results: Commonly used thiazide and thiazide-like diuretics carry resonating structural components such as sulfonamide groups that contribute to their photosensitizing activity. Overall, 13 observational studies (nine case-control studies and four cohort studies) assessed the association between the use of different thiazide or thiazide-like diuretics and the risk of several types of skin cancer. Of those, nine studies showed positive associations ranging from 3% increased risk for bendroflumethiazide and basal cell carcinoma to 311% increased risk for thiazide diuretics and squamous cell carcinoma. All studies had important design-related methodological limitations including, but not limited to, potential confounding by indication, detection bias, and time-window bias. Conclusions: Commonly used thiazide and thiazide-like diuretics have photosensitizing potential, and some observational studies with important methodological limitations have linked their use to an increased risk of skin cancer. Well-designed observational studies are needed to provide more solid evidence on this possible association.