Marc J. Gunter, PhD (*); Neil Murphy, PhD (*); Amanda J. Cross, PhD; Laure Dossus, PhD; Laureen Dartois, PhD; Guy Fagherazzi, PhD; Rudolf Kaaks, PhD; Tilman Kühn, PhD; Heiner Boeing, PhD; Krasimira Aleksandrova, PhD; Anne Tjønneland, MD, PhD; Anja Olsen, PhD; Kim Overvad, MD, PhD; Sofus Christian Larsen, PhD; Maria Luisa Redondo Cornejo, PhD; Antonio Agudo, PhD; María José Sánchez Pérez, MD, PhD; Jone M. Altzibar, PhD; Carmen Navarro, MD, PhD; Eva Ardanaz, MD, PhD; Kay-Tee Khaw, MB BChir; Adam Butterworth, PhD; Kathryn E. Bradbury, PhD; Antonia Trichopoulou, MD, PhD; Pagona Lagiou, MD, PhD; Dimitrios Trichopoulos, MD, PhD (†); Domenico Palli, MD; Sara Grioni, BSc; Paolo Vineis, MD, MPH; Salvatore Panico, MD, MSc; Rosario Tumino, MD; Bas Bueno-de-Mesquita, MD, PhD; Peter Siersema, MD, PhD; Max Leenders, PhD; Joline W.J. Beulens, PhD; Cuno U. Uiterwaal, MD, PhD; Peter Wallström, MD, PhD; Lena Maria Nilsson, PhD; Rikard Landberg, PhD; Elisabete Weiderpass, MD, PhD; Guri Skeie, PhD; Tonje Braaten, PhD; Paul Brennan, PhD; Idlir Licaj, PhD; David C. Muller, PhD; Rashmi Sinha, PhD; Nick Wareham, PhD, MBBS; Elio Riboli, MD, ScM
Note: All authors had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The authors are not affiliated with the listed funding institutions. Drs. Gunter and Murphy act as the guarantors of this article.
Acknowledgment: The authors thank the EPIC participants and staff for their valuable contribution to this research and Nicola Kerrison (MRC Epidemiology Unit, University of Cambridge) for managing the data for the InterAct Project.
Financial Support: The coordination of EPIC is financially supported by the European Commission Directorate-General for Health and Consumers and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, and Institut National de la Santé et de la Recherche Médicale (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Cancer Research, National Research Council, and Associazione Iblea per la Ricerca Epidemiologica Ragusa, Associazione Volontari Italiani Sangue Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sport, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZorgOnderzoek Nederland, World Cancer Research Fund International, and Statistics Netherlands (the Netherlands); European Research Council (grant ERC-2009-AdG 232997), NordForsk, and Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II (RD12/0036/0018) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); and Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and the Wellcome Trust (United Kingdom). Funding for the biomarker measurements in the subcohort was provided by grants to EPIC-InterAct from the European Community Framework Programme 6 and to EPIC-Heart from the Medical Research Council and the British Heart Foundation (joint award G0800270). Funding for the InterAct project was provided by the European Union Sixth Framework Programme (grant LSHM_CT_2006_037197). Dr. Muller's work was done during an International Agency for Research on Cancer Australia postdoctoral fellowship, supported by Cancer Council Australia. Dr. Palli was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro.
Disclosures: Dr. Butterworth reports grants from the European Union Framework 7, the European Research Council, the U.K. Medical Research Council, the British Heart Foundation, and the U.K. National Institute for Health Research during the conduct of the study and from Biogen, Merck, and Pfizer outside the submitted work. Dr. Beulens reports grants from Unilever R&D and FrieslandCampina outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2945.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Gunter (e-mail, firstname.lastname@example.org). Data set: Requests for the data require formal approval by the EPIC principal investigators (e-mail, email@example.com).
Requests for Single Reprints: Marc Gunter, PhD, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Gunter, Murphy, Dossus, and Brennan: International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69372 Lyon CEDEX 08, France.
Drs. Cross, Vineis, Muller, and Riboli: Department of Epidemiology and Biostatistics, Imperial College London, St. Mary's Campus, Norfolk Place, Paddington, London W2 1PG, United Kingdom.
Drs. Dartois and Fagherazzi: Gustave Roussy, Espace Maurice Tubiana, Equipe E3N/E4N, 114 rue Edouard Vaillant, 94800 Villejuif, France.
Drs. Kaaks and Kühn: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Drs. Boeing and Aleksandrova: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
Drs. Tjønneland and Olsen: Danish Cancer Society, Strandboulevarden 49, DK-2100 København Ø, Denmark.
Dr. Overvad: Aarhus University, Bartholins Allé 2, Building 1260, 2.26, 8000 Aarhus C, Denmark.
Dr. Larsen: Research Unit for Dietary Studies, The Parker Institute, Copenhagen University Hospital, Bispebjerg og Frederiksberg, Nordre Fasanvej 57, Road 8-entrance 19, DK-2000 Frederiksberg, Denmark.
Dr. Redondo Cornejo: Public Health and Health Planning Directorate, Consejería de Salud y Servicios Sanitarios del Principado de Asturias General Elorza 32, 33001 Oviedo, Spain.
Dr. Agudo: Institut Català d'Oncologia (ICO), Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Av. Gran Via de l'Hospitalet 199-203, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
Dr. Sánchez Pérez: Escuela Andaluza de Salud Pública, Cuesta del Observatorio, 4 - Campus Universitario de Cartuja s/n, Apdo. de Correos 2070 - 18080 Granada, Spain.
Dr. Altzibar: Public Health Department of Gipuzkoa, Basque Government, Avenida de Navarra, 4-20013 Donostia, San Sebastián, Spain.
Dr. Navarro: Epidemiology and Public Health Department, Murcia Health Council, Ronda de Levante 11, Murcia 3008, Spain.
Dr. Ardanaz: Epidemiology, Prevention and Promotion Health Service, Institute of Public Health Navarra, Leyre 15, 31003 Pamplona, Navarra, Spain.
Drs. Khaw and Butterworth: Department of Public Health & Primary Care, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom.
Dr. Bradbury: Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Oxford OX3 7LF, United Kingdom.
Dr. Trichopoulou: Hellenic Health Foundation, Kaisareias 13 & Alexandroupoleos, GR-115 27, Athens, Greece.
Dr. Lagiou: Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Kresge, Room 901, Boston, MA 02115.
Dr. Palli: Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Study and Prevention Centre), Via delle Oblate 2, 50141, Florence, Italy.
Ms. Grioni: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian, 1, 20133 Milano, Italy.
Dr. Panico: Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Corso Umberto I, 40, 80138 Napoli, Italy.
Dr. Tumino: Tumor Registry, Department of Preventive Medicine, Provincial Health Ragusa, Via Dante 109, 97100 Ragusa, Italy.
Dr. Bueno-de-Mesquita: RIVM, Antonie van Leeuwenhoeklaan 9, 3721 MA, Bilthoven, PO Box 1, 3720 BA Bilthoven, the Netherlands.
Drs. Siersema and Leenders: Department of Gastroenterology and Hepatology, University Medical Centre, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands.
Drs. Beulens and Uiterwaal: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Dr. Wallström: Departmental Office for Clinical Sciences, Malmö, Clinical Research Centre, Post Box 50332, SE-202 13 Malmö, Sweden.
Dr. Nilsson: Department of Public Health and Clinical Medicine, University Hospital, 901 85 Umeå, Sweden.
Dr. Landberg: Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Almas Allé 8, 750 07 Uppsala, Sweden.
Drs. Weiderpass, Skeie, Braaten, and Licaj: Fakturaadresse, UiT Norges Arktiske Universitet, Fakturamottak, Postboks 6050 Langnes, 9037 Tromsø, Norway.
Dr. Sinha: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, MSC 9776, Bethesda, MD 20892.
Dr. Wareham: MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, United Kingdom.
Author Contributions: Conception and design: M.J. Gunter, N. Murphy, H. Boeing, A. Tjønneland, M.J. Sánchez Pérez, E. Ardanaz, D. Trichopoulos, P. Vineis, R. Tumino, B. Bueno-de-Mesquita, E. Weiderpass, P. Brennan, E. Riboli.
Analysis and interpretation of the data: M.J. Gunter, N. Murphy, A.J. Cross, K. Overvad, S.C. Larsen, E. Ardanaz, A. Trichopoulou, D. Trichopoulos, J.W.J. Beulens, E. Weiderpass, G. Skeie, D.C. Muller, R. Sinha, E. Riboli.
Drafting of the article: M.J. Gunter, N. Murphy, D. Trichopoulos, D. Palli, P. Vineis, L.M. Nilsson, E. Weiderpass, R. Sinha, E. Riboli.
Critical revision of the article for important intellectual content: M.J. Gunter, N. Murphy, A.J. Cross, L. Dossus, G. Fagherazzi, R. Kaaks, K. Aleksandrova, A. Tjønneland, A. Olsen, K. Overvad, S.C. Larsen, A. Agudo, C. Navarro, E. Ardanaz, A. Butterworth, K.E. Bradbury, A. Trichopoulou, P. Lagiou, D. Trichopoulos, D. Palli, S. Panico, R. Tumino, B. Bueno-de-Mesquita, P. Siersema, J.W.J. Beulens, C.U. Uiterwaal, P. Wallström, R. Landberg, E. Weiderpass, G. Skeie, T. Braaten, P. Brennan, I. Licaj, D.C. Muller, R. Sinha, N. Wareham, E. Riboli.
Final approval of the article: M.J. Gunter, N. Murphy, A.J. Cross, L. Dossus, L. Dartois, G. Fagherazzi, R. Kaaks, T. Kühn, H. Boeing, K. Aleksandrova, A. Tjønneland, A. Olsen, K. Overvad, S.C. Larsen, M.L. Redondo Cornejo, A. Agudo, M.J. Sánchez Pérez, J.M. Altzibar, C. Navarro, E. Ardanaz, K.T. Khaw, A. Butterworth, K.E. Bradbury, A. Trichopoulou, P. Lagiou, D. Trichopoulos, D. Palli, S. Grioni, P. Vineis, S. Panico, R. Tumino, B. Bueno-de-Mesquita, P. Siersema, M. Leenders, J.W.J. Beulens, C.U. Uiterwaal, P. Wallström, L.M. Nilsson, R. Landberg, E. Weiderpass, G. Skeie, T. Braaten, P. Brennan, I. Licaj, D.C. Muller, R. Sinha, N. Wareham, E. Riboli.
Provision of study materials or patients: T. Kühn, K. Overvad, E. Ardanaz, K.T. Khaw, D. Trichopoulos, J.W.J. Beulens, E. Weiderpass, G. Skeie, N. Wareham.
Statistical expertise: N. Murphy, D. Trichopoulos, E. Weiderpass, I. Licaj, D.C. Muller.
Obtaining of funding: R. Kaaks, A. Tjønneland, K. Overvad, K.T. Khaw, D. Trichopoulos, S. Panico, R. Tumino, E. Weiderpass, N. Wareham.
Administrative, technical, or logistic support: R. Kaaks, K. Overvad, E. Ardanaz, K.T. Khaw, D. Trichopoulos, P. Vineis, B. Bueno-de-Mesquita, E. Weiderpass.
Collection and assembly of data: M.J. Gunter, R. Kaaks, T. Kühn, H. Boeing, A. Tjønneland, K. Overvad, A. Agudo, M.J. Sánchez Pérez, C. Navarro, E. Ardanaz, K.T. Khaw, K.E. Bradbury, A. Trichopoulou, P. Lagiou, D. Trichopoulos, D. Palli, S. Grioni, S. Panico, R. Tumino, B. Bueno-de-Mesquita, J.W.J. Beulens, E. Weiderpass, G. Skeie, P. Brennan, N. Wareham, E. Riboli.
The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear.
To examine whether coffee consumption is associated with all-cause and cause-specific mortality.
Prospective cohort study.
10 European countries.
521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition).
Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800).
During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels.
Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once.
Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.
European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.
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Gunter MJ, Murphy N, Cross AJ, Dossus L, Dartois L, Fagherazzi G, et al. Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study. Ann Intern Med. [Epub ahead of print 11 July 2017]:. doi: 10.7326/M16-2945
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Published: Ann Intern Med. 2017.
Cardiology, Coronary Risk Factors, Dyslipidemia, Gastroenterology/Hepatology, Hematology/Oncology.
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