Risk of basal cell carcinoma in a randomized clinical trial of aspirin and folic acid for the prevention of colorectal adenomas

BackgroundAspirin may reduce the risk of several types of cancer. ObjectivesTo evaluate if folic acid is associated with risk of basal cell carcinoma (BCC). MethodsBCC incidence was evaluated in a randomized, double-blind, placebo-controlled clinical trial of aspirin (81 mg daily or 325 mg daily for similar to 3 years) and/or folic acid (1 mg daily for similar to 6 years) for the prevention of colorectal adenomas among 1121 participants with a previous adenoma. BCC was confirmed by blinded review of pathology reports. ResultsOne hundred and four of 958 non-Hispanic white participants were diagnosed with BCC over a median follow-up of 135 years. Cumulative incidence of BCC was 12% [95% confidence interval (CI) 7-17] for placebo, 16% (95% CI 11-21) for 81 mg aspirin daily and 15% (95% CI 10-20) for 325 mg aspirin daily [hazard ratio (HR) for any aspirin 145 (95% CI 093-226); HR for 81 mg daily 157 (95% CI 096-256); HR for 325 mg daily 133 (95% CI 080-220)]. BCC risk was higher with aspirin use in those without previous skin cancer but lower with aspirin use in those with previous skin cancer (P-interaction = 002 for 81 mg aspirin daily; P-interaction = 003 for 325 mg aspirin daily). Folic acid supplementation was unrelated to BCC incidence (HR 085; 95% CI 057-127). ConclusionsNeither aspirin nor folic acid treatment had a statistically significant effect on risk of BCC. Subgroup analysis suggested that chemopreventive effects of nonsteroidal anti-inflammatory drugs may be specific to those at high risk for BCC. What's already known about this topic? Clinical trials have found that short-term oral celecoxib may reduce the risk of basal cell carcinoma (BCC) in those with multiple actinic keratoses or basal cell naevus syndrome. Observational studies have reported no association or a modest decrease in the risk of developing BCC or cutaneous squamous cell carcinoma with use of aspirin or other nonsteroidal anti-inflammatory drugs. Dietary consumption of folic acid does not appear to be linked to BCC. What does this study add? In the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled clinical trial, neither aspirin (81 mg daily or 325 mg daily for approximately 3 years) nor folic acid (1 mg daily for approximately 6 years) resulted in a statistically significant alteration in the risk of first primary BCC after randomization. Subgroup analysis revealed that the treatment effect for aspirin differed for those with and without a history of skin cancer.