title: Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.
abstract: Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1= 1.26; 95% CI 1.00-1.58; Ptrend= 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1= 1.29; 95% CI 1.02-1.62; Ptrend= 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Matejcic
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: de Batlle
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Ricci
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Biessy
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Perrier
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: I
authors.initials: I
authors.lastname: Huybrechts
authors.affiliation: Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.|Department of Community Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.|Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Institut Gustave Roussy, Villejuif, France.|Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: Institut Gustave Roussy, Villejuif, France.|Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Cadeau
authors.affiliation: Institut Gustave Roussy, Villejuif, France.|Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: His
authors.affiliation: Centre Léon Bérard, INSERM U1052, Cancer Research Center of Lyon, Lyon, France.
authors.forename: D G
authors.initials: DG
authors.lastname: Cox
authors.affiliation: Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: R T
authors.initials: RT
authors.lastname: Fortner
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: P
authors.initials: P
authors.lastname: Lagiou
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Benetou
authors.affiliation: Cancer Registry and Histopathology Unit, Civic - M.P. Arezzo Hospital, ASP Ragusa, Ragusa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Panico
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sieri
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Palli
authors.affiliation: Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy.|Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ricceri
authors.affiliation: Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.|Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: H B As
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Department of Community Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.
authors.forename: G
authors.initials: G
authors.lastname: Skeie
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Amiano
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain.|Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Chirlaque
authors.affiliation: CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.|Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.|Navarra Public Health Institute, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Barricarte
authors.affiliation: Public Health Directorate, Asturias, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Quirós
authors.affiliation: Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Buckland
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C H
authors.initials: CH
authors.lastname: van Gils
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: P H
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
authors.forename: T J
authors.initials: TJ
authors.lastname: Key
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Gylling
authors.affiliation: Department of Population Health, NYU School of Medicine, New York, NY.
authors.forename: A
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: I
authors.initials: I
authors.lastname: Romieu
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Chajès
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000737:chemistry / Q000453:epidemiology* / Q000235:genetics; D016022:Case-Control Studies; D004032:Diet; D004967:Estrogens; D005060:Europe / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000097:blood / Q000453:epidemiology*; D005500:Follow-Up Studies; D018734:Genes, erbB-2; D006801:Humans; D008019:Life Style; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011374:Progesterone; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000453:epidemiology*
chemical_list: D015415:Biomarkers; D004967:Estrogens; D011374:Progesterone; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12
keywords: MTHFR polymorphism; alcohol; breast cancer; folate; hormone receptor status; plasma biomarkers; vitamin B12