Reviewing the effects of thiazide and thiazide-like diuretics as photosensitizing drugs on the risk of skin cancer.

Background: 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.

Objective: To critically appraise in a narrative review, the association between use of thiazide and thiazide-like diuretics and risk of skin cancer.

Methods: We evaluated chemical structures and photosensitizing potential of selected thiazide and thiazide-like diuretics. Moreover, we searched PubMed up to December 2018 for observational studies assessing the association between use of thiazide or thiazide-like diuretics and risk of skin cancer. Study quality was assessed 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 (9 case-control, 4 cohort) studies assessed the association between use of different thiazide or thiazide-like diuretics and risk of several skin cancer types. 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 potential confounding by indication, detection bias, and time-window bias.

Conclusion: 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.