title: Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk.
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.
  
  
  METHODS
  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.
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Maruti
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Emily
authors.initials: E
authors.lastname: White
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D016001:Confidence Intervals; D004032:Diet; D004034:Diet Surveys; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015999:Multivariate Analysis; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012306:Risk; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D005492:Folic Acid