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Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
Nutrition and Metabolism Section, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France
Research Foundation—Flanders (FWO), 1000 Brussels, Belgium
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Hospital, London W2 1PG, UK
Diet, Genes and Environment, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark
Department of Public Health, Aarhus University, DK-8000 Aarhus C, Denmark
Department of Public Health, University of Copenhagen, DK-2200 Copenhagen, Denmark
Division of Cancer Epidemiology, German Cancer Research Center, 69120 Heidelberg, Germany
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany
Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network—ISPRO, 50139 Firenze, Italy
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Via Venezian, 1, 20133 Milano, Italy
Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital, 10126 Turin, Italy
Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), 97100 Ragusa, Italy
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands
Cancer Epidemiology Research Program, Unit of Nutrition and Cancer, Institut Català d’Oncologa, 08908 L’Hospitalet de Llobregat, Barcelona, Spain
Navarra Public Health Institute, 31003 Pamplona, Spain
IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
CIBER Epidemiology and Public Health CIBERESP, 28029 Madrid, Spain
Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, 30120 Murcia, Spain
Escuela Andaluza de Salud Pública (EASP), 18011 Granada, Spain
Instituto de Investigación Biosanitaria ibs., 18014 Granada, Spain
Department of Preventive Medicine and Public Health, University of Granada, 18016 Granada, Spain
Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, 205 02 Malmö, Sweden
Unit Pathology, Department of Medical Biosciences, Umeå Universitet, 901 85 Umeå, Sweden
Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden
Department of Surgery, Skåne University Hospital Malmö, Lund University, Bröstmottagningen, 214 28 Malmö, Sweden
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 LF7, UK
Office of the Director, International Agency for Research on Cancer, CEDEX 08, 69372 Lyon, France
Department of Public Health and Primary Care, KU Leuven, 3000 Leuven, Belgium
IDEWE (Externe dienst voor Preventie en Bescherming op het Werk), 3001 Heverlee, Belgium
Author to whom correspondence should be addressed.
Academic Editor: Stefano Realdon
Nutrients 2021, 13(6), 1843;
Received: 20 April 2021 / Revised: 25 May 2021 / Accepted: 26 May 2021 / Published: 28 May 2021
(This article belongs to the Special Issue Human Nutrition and Cancer Prevention)
(1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992–2000 and December 2013–December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association. View Full-Text
Keywords: breast cancer; folate; choline; betaine; methionine; EPIC breast cancer; folate; choline; betaine; methionine; EPIC
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MDPI and ACS Style

Van Puyvelde, H.; Papadimitriou, N.; Clasen, J.; Muller, D.; Biessy, C.; Ferrari, P.; Halkjær, J.; Overvad, K.; Tjønneland, A.; Fortner, R.T.; Katzke, V.; Schulze, M.B.; Chiodini, P.; Masala, G.; Pala, V.; Sacerdote, C.; Tumino, R.; Bakker, M.F.; Agudo, A.; Ardanaz, E.; Chirlaque López, M.D.; Sánchez, M.-J.; Ericson, U.; Gylling, B.; Karlsson, T.; Manjer, J.; Schmidt, J.A.; Nicolas, G.; Casagrande, C.; Weiderpass, E.; Heath, A.K.; Godderis, L.; Van Herck, K.; De Bacquer, D.; Gunter, M.J.; Huybrechts, I. Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Nutrients 2021, 13, 1843.

AMA Style

Van Puyvelde H, Papadimitriou N, Clasen J, Muller D, Biessy C, Ferrari P, Halkjær J, Overvad K, Tjønneland A, Fortner RT, Katzke V, Schulze MB, Chiodini P, Masala G, Pala V, Sacerdote C, Tumino R, Bakker MF, Agudo A, Ardanaz E, Chirlaque López MD, Sánchez M-J, Ericson U, Gylling B, Karlsson T, Manjer J, Schmidt JA, Nicolas G, Casagrande C, Weiderpass E, Heath AK, Godderis L, Van Herck K, De Bacquer D, Gunter MJ, Huybrechts I. Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Nutrients. 2021; 13(6):1843.

Chicago/Turabian Style

Van Puyvelde, Heleen, Nikos Papadimitriou, Joanna Clasen, David Muller, Carine Biessy, Pietro Ferrari, Jytte Halkjær, Kim Overvad, Anne Tjønneland, Renée T. Fortner, Verena Katzke, Matthias B. Schulze, Paolo Chiodini, Giovanna Masala, Valeria Pala, Carlotta Sacerdote, Rosario Tumino, Marije F. Bakker, Antonio Agudo, Eva Ardanaz, María Dolores Chirlaque López, Maria-Jose Sánchez, Ulrika Ericson, Björn Gylling, Therese Karlsson, Jonas Manjer, Julie A. Schmidt, Geneviève Nicolas, Corinne Casagrande, Elisabete Weiderpass, Alicia K. Heath, Lode Godderis, Koen Van Herck, Dirk De Bacquer, Marc J. Gunter, and Inge Huybrechts. 2021. "Dietary Methyl-Group Donor Intake and Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)" Nutrients 13, no. 6: 1843.

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