Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk

Background: Few epidemiologic studies have examined very high intakes of folate and whether consumption of nutrients involved in one-carbon metabolism is associated with breast cancer risk. Objective: We prospectively examined whether the consumption of folate and nutrients involved in one-carbon metabolism (methionine, riboflavin, and vitamins B-6 and B-12) from self-reported intakes of diet (in year before baseline) and supplements (averaged over 10 y before baseline) were associated with the incidence of breast cancer and breast cancer tumor characteristics. Design: Participants were 35,023 postmenopausal women aged 50-76 y in the VITamins And Lifestyle (VITAL) cohort study; breast cancer was diagnosed in 743 of these women between baseline (2000-2002) and 2006. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks (RRs) and 95% CIs. Results: Women consuming >= 1272 dietary folate equivalents (DFE)/d of total folate (10-y average) had a 22% decrease in breast cancer risk compared with women consuming <= 345 DFE/d (RR: 0.78; 95% CI: 0.61, 0.99; P for trend = 0.05). A greater benefit was observed for estrogen-receptor (ER) negative than for ER+ breast cancers (RR: 0.38; 95% CI: 0.18, 0.80; P for trend = 0.02; P = 0.02 for the difference between ER- and ER+). Neither current intakes of folate nor current or long-term intakes of other one-carbon nutrients were significantly associated with breast cancer risk. Multivitamin use attenuated the increased risk of breast cancer associated with alcohol drinking (P for interaction = 0.02). Conclusions: Our study of predominantly supplement users suggests that high intakes of folate averaged over 10 y do not increase breast cancer risk, but may be protective, particularly against ER- breast cancers. Am J Clin Nutr 2009; 89: 624-33.