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Nutrients 2018, 10(5), 654;

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

Department of Epidemiology, GROW School for Oncology and Developmental Biology, Maastricht University, 6229 HA Maastricht, The Netherlands
Nutritional Methodology and Biostatistics Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France
Epidaure, Prevention Department of the Institut régional du Cancer de Montpellier (ICM), 34298 Montpellier, France
Laboratoire Epsylon, Paul Valery University of Montpellier, 34090 Montpellier, France
Biomarkers Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France
Nutritional Epidemiology Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford OX3 7LF, UK
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, 50141 Florence, Italy
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Cancer Registry and Histopathology Department, Civic—M.P.Arezzo Hospital, ASP, 97100 Ragusa, Italy
Department of Clinical and Biological Sciences, University of Turin, 10124 Turin, Italy
Unit of Epidemiology, Regional Health Service ASL TO3, 10095 Turin, Italy
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, 80138 Naples, Italy
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, The Netherlands
Former Senior Scientist, Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands
Former Associate Professor, Department of Gastroenterology and Hepatology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
Visiting Professor, Dept. of Epidemiology and Biostatistics, The School of Public Health, Imperial College, London SW7 2AZ, UK
Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
Navarra Public Health Institute, 31003 Pamplona, Spain
IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
CIBER de Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, 08908 Barcelona, Spain
Public Health Directorate, 33005 Oviedo, Spain
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30008 Murcia, Spain
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18010 Granada, Spain
Basque Regional Health Department, Public Health Direction and Biodonostia Research Institute CIBERESP, 20014 Donostia, Spain
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London SW7 2AZ, UK
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, 45110 Ioannina, Greece
Danish Cancer Society Research Center, 2100 Copenhagen, Denmark
Department of Public Health, Section for Epidemiology, Aarhus University, 8000 Aarhus, Denmark
Department of Cardiology, Aalborg University Hospital, 9100 Aalborg, Denmark
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, 9019 Tromsø, Norway
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, NO-0304 Oslo, Norway
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden
Genetic Epidemiology Group, Folkhälsan Research Center, 00290 Helsinki, Finland
CESP “Health across Generations”, INSERM, Univ Paris-Sud, UVSQ, Univ Paris-Saclay, 94800 Villejuif, France
Gustave Roussy, 94800 Villejuif, France
Cancer Epidemiology Centre, Cancer Council Victoria and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC 3010, Australia
Hellenic Health Foundation, 115 27 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, 157 72 Athens, Greece
2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, 124 62 Haidari, Greece
1st Department of Critical Care Medicine & Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, 10675 Athens, Greece
Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Psychiatry, SE-221 00 Lund, Sweden
Department of Translational Medicine, Clinical Chemistry, Lund University, Skåne University Hospital, 205 02 Malmö, Sweden
Genetic Epidemiology Group, Section of Genetics, International Agency for Research on Cancer (IARC-WHO), 69372 Lyon, France
Author to whom correspondence should be addressed.
Received: 26 February 2018 / Revised: 11 May 2018 / Accepted: 17 May 2018 / Published: 22 May 2018
PDF [1215 KB, uploaded 23 May 2018]


Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions. View Full-Text
Keywords: alcohol; targeted metabolomics; lipid metabolites; amino acids; acylcarnitines alcohol; targeted metabolomics; lipid metabolites; amino acids; acylcarnitines

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Van Roekel, E.H.; Trijsburg, L.; Assi, N.; Carayol, M.; Achaintre, D.; Murphy, N.; Rinaldi, S.; Schmidt, J.A.; Stepien, M.; Kaaks, R.; Kühn, T.; Boeing, H.; Iqbal, K.; Palli, D.; Krogh, V.; Tumino, R.; Ricceri, F.; Panico, S.; Peeters, P.H.; Bueno-de-Mesquita, B.; Ardanaz, E.; Lujan-Barroso, L.; Quirós, J.R.; Huerta, J.M.; Molina-Portillo, E.; Dorronsoro, M.; Tsilidis, K.K.; Riboli, E.; Rostgaard-Hansen, A.L.; Tjønneland, A.; Overvad, K.; Weiderpass, E.; Boutron-Ruault, M.-C.; Severi, G.; Trichopoulou, A.; Karakatsani, A.; Kotanidou, A.; Håkansson, A.; Malm, J.; Weijenberg, M.P.; Gunter, M.J.; Jenab, M.; Johansson, M.; Travis, R.C.; Scalbert, A.; Ferrari, P. Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort. Nutrients 2018, 10, 654.

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