Photosensitizing Drugs and Risk of Skin Cancer in Women-A Prospective Population-Based Study

Abstract

Background: Several widely used drugs have photosensitizing properties, and much research has been conducted to find associations between their use and the risk of developing cutaneous malignant melanoma (cM), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC), often with conflicting results.

Objective: To assess whether the use of commonly prescribed photosensitizing drugs increases skin cancer risk.

Methods: Analyses were performed using a large cohort of women, with prospectively collected information on phenotypic traits and sun exposure. Comprehensive information on pharmaceutical treatments and skin cancer occurrence was obtained through national registries. Drugs with photosensitizing properties were grouped according to the Anatomical Therapeutic Chemical system in nine groups, and associations between the use of such drugs were investigated using multivariable Cox regression analysis. The number of retrieved daily doses was analyzed to test the dose-response relationship.

Results: Hormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11-1.39), cSCC (HR 1.23; 95% CI: 1.03-1.47) and cM (HR 1.31; 95% CI: 1.01-1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3-2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09-1.44) and cM (HR 1.41; 95% CI: 1.03-1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC.

Conclusions: Estrogen treatment increased the risk of all investigated skin cancers. Among those using diuretics, loop diuretics increased the risk of cSCC, and thiazide use increased the risk of BCC. We suggest that physicians should advise female patients prescribed estrogen, thiazides, or loop diuretics to limit their sun exposure.

Keywords: basal cell carcinoma; melanoma; photosensitizing drugs; prospective; squamous cell carcinoma.