Alcohol-folate interactions in women's oral cancer risk: A cohort study

Methods: Our study population included registered female nurses who enrolled in the Nurses' Health Study (NHS) in 1976. Information on alcohol intake, smoking and diet was obtained from self-reported Food Frequency Questionnaires (FFQ) every 4 years since 1980. Oral cancer was self-reported by the participants and confirmed by medical record review. Cox proportional regression analysis was conducted and multivariate hazard ratios were calculated.

Results: A total of 88798 participants were included in this analysis and were prospectively evaluated from 1980 to 2006. After exclusion of cancers reported at baseline and cancers of the lip and nasopharynx, 146 confirmed cases of oral cancer were included in the analysis. The multivariate adjusted hazard ratios and 95% confidence intervals for alcohol intake were 0.83 (0.53-1.31) for 5-14.9 grams/day intake; 1.5 (0.92-2.45) for 15-29.9 grams/day intake; and 2.48 (1.45-4.23) for ¬>30 grams/day intake, compared to 0-4.9 grams/day intake (i.e., non-drinkers or rare drinkers) when controlling for age, former alcohol drinking, smoking and folate. We observed a significant interaction between alcohol and folic acid, as higher intake of folic acid attenuates the elevated risk for oral cancer among alcohol drinkers (p value = 0.009).

Conclusions: Our analysis confirms that alcohol intake is an independent risk factor for oral cancer among women after controlling for smoking. This is the first prospective study to report a significant antagonism between alcohol intake and folate in oral cancer, a finding with potential clinical utility. Funded by NIDCR grants T32DE07151 & DE015593.