Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk2

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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.

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">Supported by the National Cancer Institute of the National Institutes of Health (grants R01 CA74846 and R25 CA94880).