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1 From the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (SSM, CCM, and EW), and the Department of Epidemiology, University of Washington, Seattle, WA (SSM, CCM, and EW).
2 Supported by the National Cancer Institute of the National Institutes of Health (grants R01 CA74846 and R25 CA94880). 3 Reprints not available. Address correspondence to E White, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109. E-mail: ewhite{at}fhcrc.org.
ABSTRACT
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.
Received for publication June 20, 2008. Accepted for publication November 17, 2008.
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