Prospective association between dietary folate intake and skin cancer risk: results from the Supplémentation en Vitamines et Minéraux Antioxydants cohort

Abstract

The role of folate in skin carcinogenesis is unclear, with experimental data suggesting potentially protective but also deleterious effects. Our main objective was to investigate the prospective association between dietary folate intake and risks of skin cancer (overall), nonmelanoma skin cancer (NMSC), and basal cell carcinoma (BCC). As an exploratory analysis, we also investigated the prospective association between erythrocyte folate concentration and skin cancer risk. In this study, we included 5880 participants in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort (follow-up: 1994-2007) who completed at least six 24-h dietary records during the first 2 y of the study. Associations between sex-specific tertiles of dietary and erythrocyte folate and skin cancer risk were assessed by using multivariate Cox proportional hazards models. After a median follow-up of 12.6 y, 144 incident skin cancers were diagnosed. Dietary folate intake was associated with increased risk of overall skin cancer [HR for tertile 3 compared with tertile 1 (HR(T3vs.T1)): 1.79; 95% CI: 1.07, 2.99; P-trend = 0.03], NMSC (HR(T3vs.T1): 1.85; 95% CI: 1.06, 3.23; P-trend = 0.03), and BCC (HR(T3vs.T1): 1.78; 0.98, 3.24; P-trend = 0.05). This association was observed in women (corresponding P-trend = 0.007, 0.009, and 0.009, respectively) but not in men (P-trend = 0.8, 0.8, and 0.9, respectively). P-interaction values between tertiles of dietary folate intake and sex were 0.04, 0.02, and 0.02 for overall skin cancer, NMSC, and BCC, respectively. Erythrocyte folate concentration was directly associated with increased risk of overall skin cancer (HR(T3vs.T1): 2.54; 95% CI: 0.95, 6.81; P-trend = 0.03), NMSC (HR(T3vs.T1): 3.49; 95% CI: 1.11, 11.0; P-trend = 0.01), and BCC (HR(T3vs.T1): 7.44; 95% CI: 1.57, 35.3; P-trend = 0.004) (men and women combined). This prospective study suggests an association between dietary folate intake and erythrocyte folate concentration and increased risk of overall skin cancer, NMSC, and BCC. Although several mechanistic hypotheses and 2 previous large prospective studies on BCC are in line with these results, epidemiologic literature is limited, and future research is needed to better elucidate the potential role of folate in the cause of skin cancers.