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 > or =1272 dietary folate equivalents (DFE)/d of total folate (10-y average) had a 22% decrease in breast cancer risk compared with women consuming < or =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.