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Int J Cancer. 2017 Mar 15;140(6):1246-1259. doi: 10.1002/ijc.30536.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

Author information

1
International Agency for Research on Cancer, Lyon, France.
2
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
3
Department of Community Medicine, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.
4
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
5
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
6
Institut Gustave Roussy, Villejuif, France.
7
Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France.
8
Centre Léon Bérard, INSERM U1052, Cancer Research Center of Lyon, Lyon, France.
9
Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
10
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
11
Hellenic Health Foundation, Athens, Greece.
12
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.
13
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
14
Cancer Registry and Histopathology Unit, Civic - M.P. Arezzo Hospital, ASP Ragusa, Ragusa, Italy.
15
Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, Naples, Italy.
16
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
17
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
18
Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy.
19
Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, Italy.
20
Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
21
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
22
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
23
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
24
Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain.
25
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
26
Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
27
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
28
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
29
Navarra Public Health Institute, Pamplona, Spain.
30
Public Health Directorate, Asturias, Spain.
31
Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
32
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
33
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.
34
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
35
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
36
Department of Population Health, NYU School of Medicine, New York, NY.

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.

KEYWORDS:

MTHFR polymorphism; alcohol; breast cancer; folate; hormone receptor status; plasma biomarkers; vitamin B12

PMID:
27905104
DOI:
10.1002/ijc.30536
[Indexed for MEDLINE]
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