Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women

Objective Adequate folate intake may be important for breast cancer prevention. Its protective effect may be influenced by factors associated with folate metabolism. We sought to evaluate folate intake in relation to breast cancer risk and examine whether the relation is affected by alcohol and intake of vitamin B-2 and B-12. Methods A prospective cohort analysis of folate intake was conducted among 62,739 postmenopausal women in the French E3N cohort who had completed a validated food frequency questionnaire in 1993. During nine years' follow-up, 1,812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized in quintiles and energy-adjusted using the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known breast cancer determinants. Results The multivariate RR for extreme quintiles of folate intake was 0.78 (95% CI: 0.67-0.90; p-trend = 0.001) [Median intake for Q(1) = 296 mu g/day and Q(5) = 522 mu g/day]. There was no evidence to support effect modification by alcohol or B-2 intake. The decreasing trend was most marked in women with higher folate and vitamin B-12 intake. However, test for interaction was not statistically significant (p = 0.29). Conclusions High folate intake was associated with decreased breast cancer risk. Vitamin B-12 intake may modify this association.