Folate and other one-carbon metabolism-related nutrients and risk of postmenopausal breast cancer in the Cancer Prevention Study II Nutrition Cohort

Background: Epidemiologic studies of the association of folate intake with breast cancer risk have been inconclusive, and few have investigated how related nutrients modify this association. Objective: We investigated the association of dietary (food folate plus folic acid from fortification) and total folate (food folate, folic acid from fortification, and folic acid from supplements), vitamin B-6, vitamin B-12, methionine, and alcohol intakes with postmenopausal breast cancer among women in the Cancer Prevention Study II Nutrition Cohort. The modification of the folate associations by the other nutrients was also investigated. Design: This prospective cohort study included 70,656 postmenopausal women for whom dietary information was collected in 1992. Of these, 3898 developed breast cancer between enrollment in 1992 and June 2005. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard rate ratios and 95% CIs. Results: Compared with the lowest quintile, the highest quintile of dietary folate intake was associated with a higher risk of breast cancer (rate ratio: 1.12; 95% CI: 1.01, 1.24). However, the test for trend was not significant (P for trend = 0.15). No association was found for total folate, vitamin B-6, or vitamin B-12, but methionine was inversely associated with breast cancer risk (P for trend = 0.04). The association of dietary folate with breast cancer was not modified by other nutrients or alcohol. Conclusions: This study suggests that dietary folate intake may be positively associated with postmenopausal breast cancer. However, no dose-response relation was observed. The extent to which increased supplement use and folate fortification contributes to breast cancer risk warrants further research. Am J Clin Nutr 2010;91: 1708-15.