Dietary folate consumption and risk of ovarian cancer: a prospective cohort study.

Deficient dietary folate intake may be associated with increased cancer risk in humans owing to DNA damage resulting from impaired nucleotide excision repair. It is conceivable that an association with folate may be modified by alcohol and/or methionine intake given that alcohol consumption and low methionine intakes both increase dietary folate requirements. In the cohort study reported here, we examined the association between dietary folate intake and ovarian cancer risk, overall and within strata defined by alcohol and methionine intakes. The investigation was conducted in 49 613 Canadian women who were participants in the National Breast Screening Study and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to cancer and national mortality databases yielded data on cancer incidence and deaths among cohort members, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 264 incident ovarian cancer cases among 48 766 women for whom data were available. Dietary folate intake was associated with a 25% decrease in risk of ovarian cancer for the highest versus the lowest quartile level of intake (hazard ratio=0.75, 95% confidence interval=0.42-1.34, Ptrend=0.25). On stratification by alcohol intake, dietary folate was not associated with ovarian cancer risk among women consuming <4 g/day of alcohol, but there was some suggestion of reduced risk at relatively high levels of folate intake among women consuming > or =4 g/day of alcohol/day (Ptrend=0.09; Pinteraction=0.22). The association between folate and ovarian cancer risk did not vary by strata of methionine intake (Pinteraction=0.98). Our findings, while not statistically significant, suggest that relatively high dietary folate intake may be associated with a reduction in ovarian cancer risk among women with relatively high alcohol consumption and among those with relatively high methionine intake.