title: Micronutrients Involved in One-Carbon Metabolism and Risk of Breast Cancer Subtypes.
abstract: BACKGROUND
  Vitamins involved in one-carbon metabolism are hypothesized to influence breast cancer (BC) risk. However, epidemiologic studies that examined associations between B vitamin intake and BC risk have provided inconsistent results. We prospectively examined, in the Italian ORDET cohort, whether B vitamin consumption was associated with risk of BC and BC subtypes.
  
  
  METHODS
  After a mean follow-up of 16.5 years, 391 BCs were diagnosed among 10,786 cohort women. B vitamin intakes were estimated from food frequency questionnaires. Cox proportional hazard models adjusted for energy intake and confounders, estimated hazard ratios (HR) with 95% confidence intervals (CIs) for BC according to intake.
  
  
  RESULTS
  RRs were 0.61 (95% CI 0.38-0.97 highest vs. lowest quartile; P trend 0.025) for thiamine; 0.48 (95% CI 0.32-0.71; P trend <0.001) for riboflavin; 0.59 (95% CI 0.39-0.90; P trend 0.008) for vitamin B6, and 0.65 (95% CI 0.44-0.95; P trend 0.021) for folate. As regards risk of BC subtypes, high riboflavin and folate were significantly associated with lower risk of estrogen receptor positive (ER+) and progesterone receptor positive (PR+) cancers, and high thiamine was associated with lower risk of ER-PR- cancers. High riboflavin was associated with lower risk of both HER2+ and HER2- cancers, high folate with lower risk of HER2- disease, and high thiamine with HER2+ disease.
  
  
  CONCLUSIONS
  These findings support protective effects of thiamine and one-carbon metabolism vitamins (folate, riboflavin, and vitamin B6) against BC in general; while folate may also protect against ER+PR+ and HER2- disease; and thiamine against ER-PR-, and HER2+ disease.
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cancarini
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Agnoli
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Grioni
authors.affiliation: Department of Medical Sciences, University of Torino and Human Genetics Foundation (HuGeF), Turin, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pala
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Samuele
authors.initials: S
authors.lastname: Pedraglio
authors.affiliation: Department of Preventive and Predictive Medicine, Environmental Epidemiology Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Contiero
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Riva
authors.affiliation: Department of Oncology, Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
authors.affiliation: Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D002244:Carbon / Q000378:metabolism*; D004435:Eating; D002149:Energy Intake; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018977:Micronutrients; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D002244:Carbon; D018977:Micronutrients; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human