Alcohol-folate interactions in the risk of oral cancer in women: A prospective cohort study

Background: The aim of this cohort study was to quantify the effect of alcohol on the risk of oral cancer in different strata of folate intake, controlling for known confounders. Methods: A cohort of 87,621 women in the Nurses' Health Study was followed up from 1980 to 2006, and 147 incident oral cancer cases were reported and confirmed. Data on alcohol intake and diet were obtained through self-reported food frequency questionnaires every 4 years. Cox proportional regression analysis was conducted to estimate the adjusted risk ratios (RR) and 95% confidence intervals (95% CI). Results: When compared with nondrinkers, the adjusted RRs (95% CIs) for alcohol intake were 0.59 (0.39-0.87) for 0.1-14.9 g/d, 1.15 (0.67-1.97) for 15-29.9 g/d, and 1.92 (1.08-3.40) for ≥30 g/d. We observed a significant interaction between alcohol and folate intakes (P = 0.02). The cancer risk for subjects with high alcohol (≥30 g/d) and low folate (<350 μg/d) intakes was significantly elevated (RR, 3.36; 95% CI, 1.57-7.20) as compared with nondrinkers with low folate intake. The risk associated with high alcohol intake (≥30 g/d) was reduced to 0.98 (0.35-2.70) in the high-folate (≥350 μg/d) group as compared with nondrinkers with high folate intake. Conclusions: High alcohol intake is associated with significantly increased oral cancer risk, especially in women with low folate intake. Impact: A significant interaction between alcohol and folate intakes seems to affect oral cancer risk in women, a finding with potential public health utility.