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1. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author

Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium für Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository

Subjects
Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract

Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

Published
2019
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2. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

Author

Magritt Brustad, Veronika Fedirko, Marc J. Gunter, Anja Olsen, Antonia Trichopoulou, Geneviève Nicolas, Anna Karakatsani, Veronique Chajes, Gianluca Severi, Elom K. Aglago, Eva Ardanaz, Aurora Perez-Cornago, Kim Overvad, Cristina Lasheras, Salvatore Panico, Verena Katzke, Bas Bueno-de-Mesquita, José María Huerta, Neil Murphy, Christina C. Dahm, Maria Wennberg, Teresa Norat, Bodil Ohlsson, Elisabete Weiderpass, Antonio Agudo, Heather Ward, Anne Tjønneland, Valeria Pala, Tilman Kühn, Bethany Van Guelpen, Guri Skeie, Rosario Tumino, María José Sánchez, A. M. May, Corinne Casagrande, Jeroen W.G. Derksen, Marie-Christine Boutron-Ruault, Elio Riboli, Agnès Fournier, Sophie Hellstrand, Inge Huybrechts, Georgia Martimianaki, Alessio Naccarati, Tobias Pischon, Amanda J. Cross, Pilar Amiano, Domenico Palli, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), RD06/0020 6236 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: C570/A16491, C8221/A19170, MR/M012190/1 National Research Council, NRC Medical Research Council, MRC British Heart Foundation, BHF Cancer Research UK, CRUK World Cancer Research Fund, WCRF: WCRF 2013/1002 Food Standards Agency, FSA Stroke Association European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Stavros Niarchos Foundation, SNF Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Associazione Iblea per la Ricerca Epidemiologica, AIRE Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Fondation Gustave Roussy Hellenic Health Foundation, HHF, Funding Supported by a grant from the World Cancer Research Fund ( WCRF ) to Marc Gunter (grant number: WCRF 2013/1002 ). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer . The national cohorts are supported by 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 ( INSERM ) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), and Federal Ministry of Education and Research ( BMBF ) (Germany), Hellenic Health Foundation , Stavros Niarchos Foundation , and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer ( AIRC ), National Research Council , and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu ( AVIS ) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry ( NKR ), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), and Statistics Netherlands (the Netherlands), Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), 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 ( ISCIII RETIC) ( RD06/0020 ) (Spain), Swedish Cancer Society , Swedish Scientific Council , and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK , Medical Research Council , Stroke Association , British Heart Foundation , Department of Health , Food Standards Agency , the Wellcome Trust (UK), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Subjects
Colorectal cancer, [SDV]Life Sciences [q-bio], Àcids grassos insaturats, Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Càncer colorectal, Fatty Acids, Omega-3, Medicine, Animals, Humans, Prospective Studies, 2. Zero hunger, chemistry.chemical_classification, Unsaturated fatty acids, Epidemiologic, Gastroenterology & Hepatology, Hepatology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Gastroenterology, Fishes, 1103 Clinical Sciences, Odds ratio, medicine.disease, Eicosapentaenoic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diet, chemistry, Seafood, Docosahexaenoic acid, 030220 oncology & carcinogenesis, Omega 3, Cohort, Colonic Neoplasms, Tumorigenesis, 030211 gastroenterology & hepatology, Docosapentaenoic acid, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Polyunsaturated fatty acid
Abstract

Background & Aims There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.

Published
2020
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3. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author

Eva Ardanaz, Agnetha Linn Rostgaard-Hansen, Alessio Naccarati, Elisabete Weiderpass, Pekka Keski-Rahkonen, Rudolf Kaaks, Tilman Kühn, Anna Winkvist, Jośe Mariá Huerta, H. B. Bueno-De-Mesquita, Guri Skeie, Pietro Ferrari, Krasimira Aleksandrova, Gabriel Perlemuter, Augustin Scalbert, Olatz Mokoroa, Giovanna Tagliabue, Marc J. Gunter, Kim Overvad, José Ramón Quirós, Agneta Kiss, Marie-Christine Boutron-Ruault, Yahya Mahamat-Saleh, Talita Duarte-Salles, Nivonirina Robinot, Anne Tjønneland, Antonia Trichopoulou, Julie A. Schmidt, Christina C. Dahm, Roel Vermeulen, Rosario Tumino, Núria Sala, Joseph A. Rothwell, Sophia Harlid, Magdalena Stepien, Klas Sjöberg, Vivian Viallon, Neil Murphy, Anna Karakatsani, Salvatore Panico, Nicholas J. Wareham, María José Sánchez, Francesca Mancini, Domenico Palli, Mazda Jenab, Elio Riboli, Bodil Ohlsson, Kay-Tee Khaw, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National Du Cancer, INCa: 2014-1-RT-02-CIRC-1 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Cancer Research UK, CRUK: C570/A16491 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS National Research Council, NRC 6236 Hellenic Health Foundation, HHF Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, CIRC Associazione Italiana per la Ricerca sul Cancro, AIRC RD06/0020 Deutsche Krebshilfe World Cancer Research Fund, WCRF Cancerfonden Medical Research Council, MRC: MR/M012190/1, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA) (grant number 2014-1-RT-02-CIRC-1, PI: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO), and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 for EPIC-Norfolk and C570/A16491 for EPIC-Oxford) and the Medical Research Council (1000143 for EPIC-Norfolk and MR/M012190/1 for EPIC-Oxford) (UK). The funding sources had no influence on the design of the study, the collection, analysis, and interpretation of data, the writing of the report, and or the decision to submit the paper for publication. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, prospective observational cohort, Glycocholic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, Prospective Studies, Aged, Hepatitis, business.industry, Liver Neoplasms, Cancer, Feeding Behavior, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, untargeted metabolomics, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, business, Metabolic Networks and Pathways, Chromatography, Liquid, Cohort study
Abstract

International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Published
2020
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4. Parity, breastfeeding and risk of coronary heart disease:A pan-European case-cohort study

Author

Kim Overvad, Eleni Klinaki, Elisabete Weiderpass, Emanuele Di Angelantonio, Giuseppe Matullo, Giovanna Masala, Anna Winkvist, Simon G. Thompson, M. Luisa Redondo, Françoise Clavel-Chapelon, Isabel Drake, Elena Molina-Portillo, N. Charlotte Onland-Moret, Therese Haugdahl Nøst, Adam S. Butterworth, Salma Butt, Diana Gavrila, Conchi Moreno-Iribas, Vassiliki Benetou, Antonia Trichopoulou, Tilman Kühn, Anja Olsen, Melissa A. Merritt, Ioanna Tzoulaki, Anne Tjønneland, Angela M. Wood, Larraitz Arriola, Renée Turzanski-Fortner, Fabrice Bonnet, Elio Riboli, Rosario Tumino, Karel G.M. Moons, Sanne A.E. Peters, Patrik Wennberg, Heiner Boeing, Timothy J. Key, Yvonne T. van der Schouw, Camille Lassale, Nicholas J. Wareham, Michael J. Sweeting, Salvatore Panico, Vittorio Krogh, John Danesh, Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, University Medical Center [Utrecht], Department of Public Health & Primary Care, University of Cambridge [UK] (CAM), Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Instituto de Investigación Sanitaria Biodonostia - San Sebastián, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Hellenic Health Foundation, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Clinical Sciences, Lund University [Lund], Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIBER de Epidemiología y Salud Pública (CIBERESP), Cancer Epidemiology Unit, University of Oxford-Cancer Epidemiology Unit, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Biomarkers Research, Imperial College School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Institute for Scientific Interchange Foundation, Universidad de Granada = University of Granada (UGR), Public Health Institute of Navarra, Pamplona, Spain, and CIBER Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Department of Clinical Epidemiology, Aarhus University Hospital, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Public Health Directorate Asturias, Bureau of Epidemiologic Research, Academy of Athens, Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Imperial College London, Umeå University, Medical Research Council Epidemiology Unit, European Union [HEALTH-F2-2012-279233], European Research Council [268834], Swedish Scientific Council, Regional Government of Skane and Vasterbotten (Sweden), Compagnia di San Paolo, Human Genetics Foundation-Torino (HuGeF), UK Medical Research Council [G0800270, MR/L003120/1, MR/M012190/1], British Heart Foundation [SP/09/002, RG/08/014, RG13/13/30194], UK National Institute of Health Research, Regional Government of Asturias, Cancer Research UK [570/A16491], Sicilian Government, AIRE ONLUS Ragusa, AVIS Ragusa, Swedish Cancer Society, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Gustave Roussy (IGR), University of Oxford [Oxford]-Cancer Epidemiology Unit, University of Turin, Universidad de Granada (UGR), University of Naples Federico II, Wood, Angela [0000-0002-7937-304X], Sweeting, Michael [0000-0003-0980-8965], Thompson, Simon [0000-0002-5274-7814], Di Angelantonio, Emanuele [0000-0001-8776-6719], Wareham, Nicholas [0000-0003-1422-2993], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Apollo - University of Cambridge Repository, Peters, Sanne Ae, van der Schouw, Yvonne T, Wood, Angela M, Sweeting, Michael J, Moons, Karel Gm, Weiderpass, Elisabete, Arriola, Larraitz, Benetou, Vassiliki, Boeing, Heiner, Bonnet, Fabrice, Butt, Salma T, Clavel Chapelon, Françoise, Drake, Isabel, Gavrila, Diana, Key, Timothy J, Klinaki, Eleni, Krogh, Vittorio, Kühn, Tilman, Lassale, Camille, Masala, Giovanna, Matullo, Giuseppe, Merritt, Melissa, Molina Portillo, Elena, Moreno Iribas, Conchi, Nøst, Therese H, Olsen, Anja, Onland Moret, N. Charlotte, Overvad, Kim, Panico, Salvatore, Redondo, M. Luisa, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Turzanski Fortner, Renée, Tzoulaki, Ioanna, Wennberg, Patrik, Winkvist, Anna, Thompson, Simon G, Di Angelantonio, Emanuele, Riboli, Elio, Wareham, Nicholas J, Danesh, John, Butterworth, Adam S., Commission of the European Communities, and Jonchère, Laurent

Subjects
Pediatrics, breastfeeding, coronary heart disease, Parity, Women, Epidemiology, Cardiology and Cardiovascular Medicine, Breastfeeding, Coronary Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, Pregnancy, Risk Factors, Medicine, 030212 general & internal medicine, Prospective Studies, Age of Onset, Prospective cohort study, number, Incidence, Hazard ratio, health, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Europe, Breast Feeding, Population Surveillance, Female, pregnancy, women, Cohort study, Adult, medicine.medical_specialty, life-style, lactation, Risk Assessment, Article, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Journal Article, Humans, cancer, maternal cardiovascular-disease, Proportional hazards model, business.industry, duration, mortality, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Breast feeding, Demography, Follow-Up Studies, Forecasting
Abstract

Objective: There is uncertainty about the direction and magnitude of the associations between parity, breastfeeding and the risk of coronary heart disease (CHD). We examined the separate and combined associations of parity and breastfeeding practices with the incidence of CHD later in life among women in a large, pan-European cohort study. Methods: Data were used from European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD, a case–cohort study nested within the EPIC prospective study of 520,000 participants from 10 countries. Information on reproductive history was available for 14,917 women, including 5138 incident cases of CHD. Using Prentice-weighted Cox regression separately for each country followed by a random-effects meta-analysis, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD, after adjustment for age, study centre and several socioeconomic and biological risk factors. Results: Compared with nulliparous women, the adjusted HR was 1.19 (95% CI: 1.01–1.41) among parous women; HRs were higher among women with more children (e.g., adjusted HR: 1.95 (95% CI: 1.19–3.20) for women with five or more children). Compared with women who did not breastfeed, the adjusted HR was 0.71 (95% CI: 0.52–0.98) among women who breastfed. For childbearing women who never breastfed, the adjusted HR was 1.58 (95% CI: 1.09–2.30) compared with nulliparous women, whereas for childbearing women who breastfed, the adjusted HR was 1.19 (95% CI: 0.99–1.43). Conclusion: Having more children was associated with a higher risk of CHD later in life, whereas breastfeeding was associated with a lower CHD risk. Women who both had children and breastfed did have a non-significantly higher risk of CHD.

Published
2016
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5. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Author

Amanda J. Cross, Petra H.M. Peeters, Pietro Ferrari, Françoise Clavel-Chapelon, Salvatore Panico, Augustin Scalbert, Anja Olsen, José María Huerta, Paolo Vineis, Gianluca Severi, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Bénédicte Elena-Herrmann, Nicholas J. Wareham, Pagona Lagiou, Talita Duarte-Salles, Christina Bamia, Anne Tjønneland, Rudolf Kaaks, Bodil Ohlsson, Magdalena Stepien, Antonio Agudo, Krasimira Aleksandrova, Heiner Boeing, Isabelle Romieu, Kay-Tee Khaw, Veronika Fedirko, Domenico Palli, Julie A. Schmidt, Anne Fages, Rosario Tumino, Valeria Pala, Anna Floegel, Dimitrios Trichopoulos, Miren Dorronsoro, Marc J. Gunter, Klas Sjöberg, Clément Pontoizeau, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Tilman Kühn, Elio Riboli, Mazda Jenab, Antonia Trichopoulou, Esther Molina-Montes, Fages, Anne, Duarte Salles, Talita, Stepien, Magdalena, Ferrari, Pietro, Fedirko, Veronika, Pontoizeau, Clément, Trichopoulou, Antonia, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Clavel Chapelon, Françoise, Boutron Ruault, Marie Christine, Severi, Gianluca, Kaaks, Rudolf, Kuhn, Tilman, Floegel, Anna, Boeing, Heiner, Lagiou, Pagona, Bamia, Christina, Trichopoulos, Dimitrio, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. Ba, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Molina Montes, Esther, Huerta, José María, Ardanaz, Eva, Dorronsoro, Miren, Sjöberg, Kla, Ohlsson, Bodil, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Schmidt, Julie A, Cross, Amanda, Gunter, Marc, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Elena Herrmann, Benedicte, Jenab, Mazda, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ISA - Centre de RMN à très hauts champs, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), parent, International Agency for Cancer Research (IACR), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Institute of Cancer Epidemiology, Danish Cancer Society, Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition, Harvard School of Public Health, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Nutritional Epidemiology Unit, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-IRCCS Foundation, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Community Medicine, University of Tromsø (UiT), Department of Research, Cancer Registry of Norway-Samfundet Folkhälsan, Helsinki, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet [Stockholm], Institut Català d'Oncologia, Spain Institute of Oncology, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Murcia Regional Health Council, Sección de Epidemiología de Enfermedades No Transmisibles, Navarre Public Health Institute, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Volvo, VOLVO-VOLVO, Skane University Hospital [Lund], University of Cambridge School of Clinical Medicine, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford [Oxford], Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Chemistry, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, Biomarkers Group, Nutrition and Metabolism Section, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA, grant number 2009-139, PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), European Research Council (ERC, grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skane and Vasterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 'Civile M. P. Arezzo' Hospital, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), [Fages,A, Pontoizeau,C, Elena-Herrmann,B] Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, Villeurbanne, France. [Duarte-Salles,T, Stepien,M, Ferrari,P, Scalbert,A, Romieu,I, Jenab,M] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Aleksandrova,K, Floegel,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M] INSERM, Centre for Research in Epidemiology and Population Health (CESP), nutrition, Hormones and Women’s Health Team, Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Severi,G, Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Kaaks,R, Kuhn,T] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Bamia,C] Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P, Peeters,PH] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,HB, Cross,A, Gunter,M, RibolI,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Agudo,A] Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Montes,E, Huerta,JM, Ardanaz, E] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Sjöberg,K] Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Travis,RC, Schmidt,JA] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., This work was supported by the French National Cancer Institute (L’Institut National du Cancer, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), University of Naples Federico II = Università degli studi di Napoli Federico II, and University of Oxford

Subjects
Oncology, Male, Neoplasias Hepáticas, Cirrhosis, Magnetic Resonance Spectroscopy, Epidemiology, Hepatocellular carcinoma, Nuclear magnetic resonance, Cohort Studies, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, CIRRHOSIS, Early Detection of Cancer, Medicine(all), 0303 health sciences, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings], Liver Neoplasms, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], Metabolómica, Estudios Prospectivos, General Medicine, Middle Aged, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Liver Neoplasm, 030220 oncology & carcinogenesis, Female, Liver cancer, Case-Control Studie, Life Sciences & Biomedicine, Metabolomics, Carcinoma Hepatocelular, Research Article, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], TISSUE METABOLOMICS, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Metabolomic, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus [Medical Subject Headings], Càncer de fetge, 03 medical and health sciences, Medicine, General & Internal, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, IDENTIFY SERUM BIOMARKERS, Internal medicine, General & Internal Medicine, medicine, Humans, Obesity, Epidemiologia, 030304 developmental biology, FATTY LIVER-DISEASE, Aged, Hepatitis, Science & Technology, business.industry, Case-control study, METABONOMICS, Cancer, MASS-SPECTROMETRY, medicine.disease, NMR, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Case-Control Studies, DISCOVERY, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Immunology, RISK-FACTORS, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer., This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by 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 (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).

Published
2015
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6. Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study

Author

Domenico Palli, Aurelio Barricarte, José Ramón Quirós, Laureen Dartois, Heather Ward, Salvatore Panico, Isabelle Romieu, Veronika Fedirko, Ulrika Ericson, Kim Overvad, Miren Dorronsoro, Pagona Lagiou, Krasimira Aleksandrova, Rudolf Kaaks, Kay-Tee Khaw, Anne Tjønneland, Elio Riboli, Laure Dossus, Sabina Rinaldi, Ingrid Ljuslinder, Genevieve Buckland, Marc J. Gunter, Petra H.M. Peeters, Vittorio Krogh, Alessio Naccarati, Ingegerd Johansson, Bodil Ohlsson, Peter D. Siersema, Kathryn E. Bradbury, Heiner Boeing, María José Sánchez, Mazda Jenab, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Tobias Pischon, Sven Knüppel, Teresa Norat, Nicholas J. Wareham, Joyce Kong, Dora Romaguera, Kuanrong Li, Dimitrios Trichopoulos, Rosario Tumino, Marie-Christine Boutron-Ruault, María Dolores Chirlaque, [Aleksandrova,K, Knüppe,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Jenab,M, Fedirko,V, Rinald,S, Romieu,I, Kong,J] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands. [Bueno-de-Mesquita,HB, Norat,T, Romaguera,D, Peeters,PHM, Gunter,MJ, Ward,HA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Romaguera,D] Instituto de Investigacion Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Univ Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Li,K] Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Tjønneland,K] Diet, Genes and Environment Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Sánchez,MJ, Chirlaque,M] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Bradbury,KE] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'M.P.Arezzo' Hospital, Ragusa, Italy. [Naccarati,A] HuGeF - Human Genetics Foundation – Torino, Molecular and Genetic Epidemiology Unit, Turin, Italy. [Panico,S] Department of clinical and experimental medicine-Federico II University, Naples, Italy. [Peeters,PHM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherland. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Umeå University, Umeå, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. [Weiderpass,E, Skeie,G, Borch,KB] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland., The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l¿Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom)., Aleksandrova, Krasimira, Pischon, Tobia, Jenab, Mazda, Bueno de Mesquita, H. Ba, Fedirko, Veronika, Norat, Teresa, Romaguera, Dora, Knüppel, Sven, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Kaaks, Rudolf, Li, Kuanrong, Tjønneland, Anne, Overvad, Kim, Quirós, José Ramón, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Chirlaque, Maria Dolore, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nicholas J, Bradbury, Kathryn E, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Siersema, Peter D, Peeters, Petra H. M, Ljuslinder, Ingrid, Johansson, Ingegerd, Ericson, Ulrika, Ohlsson, Bodil, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Rinaldi, Sabina, Romieu, Isabelle, Kong, Joyce, Gunter, Marc J, Ward, Heather A, Riboli, Elio, and Boeing, Heiner

Subjects
Male, consumo de alcohol, Health Behavior, 0302 clinical medicine, estudios prospectivos, European Prospective Investigation into Cancer and, Prospective Studies, estudios de cohortes, mediana edad, PROPORTION, anciano, education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, COLON-CANCER, Hazard ratio, lifestyle factors, General Medicine, adulto, 3. Good health, estilo de vida, 030220 oncology & carcinogenesis, Cohort, acrylamide, Dieta, Cohort study, Human, medicine.medical_specialty, Alcohol Drinking, European Continental Ancestry Group, Lifestyles, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], European Prospective Investigation into Cancer and Nutrition (EPIC), Endocrinology and Diabetes, dietary questionnaires, haemoglobin adducts, incidencia, White People, 03 medical and health sciences, Càncer colorectal, population attributable risks, Humans, education, Life Style, METAANALYSIS, Aged, Cancer och onkologi, Science & Technology, Proportional hazards model, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, biomarkers, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], PREVENTION, Prospective Studie, MYOCARDIAL-INFARCTION, ATTRIBUTABLE RISK, Cardiovascular and Metabolic Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], RISK-FACTORS, Proportional Hazards Model, grupo de ascendencia continental europea, measurement errors, Gerontology, colorectal cancer, combined impact, modelos de riesgos proporcionales, humanos, Colorectal Neoplasm, Cohort Studies, Risk Factors, Neoplasias colorrectales, Hábito de fumar, 030212 general & internal medicine, Prospective cohort study, conducta sanitaria, Medicine(all), Consumo de alcohol, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, NUTRITION, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Research Article, Adult, Estils de vida, neoplasias colorrectales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], smoking, Medicine, General & Internal, General & Internal Medicine, Internal medicine, medicine, factores de riesgo, Proportional Hazards Models, Nutrition (EPIC), RECTAL CANCERS, business.industry, Risk Factor, Diet, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Attributable risk, Cohort Studie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract

Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend, The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).

Published
2014
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7. The Association between Dietary Energy Density and Type 2 Diabetes in Europe: Results from the EPIC-InterAct Study

Author

InterAct Consortium, Saskia W van den Berg, Daphne L van der A, Annemieke M W Spijkerman, Geertruida J van Woudenbergh, Mariken J Tijhuis, Pilar Amiano, Eva Ardanaz, Joline W J Beulens, Heiner Boeing, Françoise Clavel-Chapelon, Francesca L Crowe, Blandine de Lauzon-Guillain, Guy Fagherazzi, Paul W Franks, Heinz Freisling, Carlos Gonzalez, Sara Grioni, Jytte Halkjaer, José María Huerta, Inge Huybrechts, Rudolf Kaaks, Kay Tee Khaw, Giovanna Masala, Peter M Nilsson, Kim Overvad, Salvatore Panico, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, María-José Sánchez, Matthias B Schulze, Nadia Slimani, Ellen A Struijk, Anne Tjonneland, Rosario Tumino, Stephen J Sharp, Claudia Langenberg, Nita G Forouhi, Edith J M Feskens, Elio Riboli, Nicholas J Wareham, The InterAct Consortium, [van den Berg,SW, van der A,DL, Spijkerman,AMW, Tijhuis,MJ] Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [van Woudenbergh,GJ, Feskens,EJM] Division of Human Nutrition - Section Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands. [Amiano,P] Instituto BIO-Donostia, Basque Government, Donostia, Spain. [Amiano,P, Ardanaz,E, Huerta,JM, Sánchez,M] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, San Sebastian, Spain. [Ardanaz,E] Navarre Public Health Institute (ISPN), Pamplona, Spain. [Beulens,JWJ, Struijk,EA] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Clavel-Chapelon,F, Fagherazzi,G] Nutrition, Hormones and Women’s Health, Institut National de la Santé et de la Recherche Médicale (INSERM) and Center for Research in Epidemiology and Population Health (CESP), Villejuif, France. [Clavel-Chapelon,F, de Lauzon-Guillain,B, Fagherazzi,G] University Paris Sud, Villejuif, France. [Crowe,FL] Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. [de Lauzon- Guillain,B] Institut National de la Santé et de la Recherche Médicale (INSERM) and Center for Research in Epidemiology and Population Health (CESP), Villejuif, France. [Franks,PW] Department of Clinical Sciences, Skane University Hospital, Lund University, Malmö, Sweden. [Rolandsson,O] Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden. [Freisling,H, Huybrechts,I] International Agency for Research on Cancer, Lyon, France. [Gonzalez,C] Unit Nutrition, Environment and Cancer, Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain. [Grioni,S] Nutritional Epidemiology Unit, Milan, Italy. [Halkjaer,J, Tjonneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Nilsson,PM] Department of Clinical Sciences Medicine, University Hospital Scania, Lund University, Malmö, Sweden. [Overvad,K] Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Overvad,K] Department of Epidemiology, School of Public Health, Aarhus, Denmark. [Panico,S] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Quirós,JR] Asturias Health & Health Care Council, Oviedo, Spain. [Sacerdote,C] Human Genetic Foundation (HuGeF), Torino, Italy. Center for Cancer Prevention, Torino, Italy. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Schulze,MB] Department of Molecular Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. [Slimani,N] Dietary Exposure Assessment Group (DEX), International Agency for Research on Cancer, Lyon, France. [Tumino,R] Cancer Registry and Histopathology Unit, Ragusa, Italy. Aire Onlus, Ragusa, Spain. [Sharp,SJ, Langenberg,C, Forouhi,NG, Wareham,NJ] MRC Epidemiology Unit, Cambridge, United Kingdom. [Riboli,E] Department of Epidemiology and Biostatistics, Imperial College London, London, UK., The EPIC-InterAct Study received funding from the European Union (Integrated project LSHM-CT-2006-037197 in the Framework Programme 6 of the European Community). DLvdA: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, AMWS: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, EA: Health Research Fund (FIS) of the Spanish Ministry of Health, Navarre Regional Government and CIBER Epidemiologı´a y Salud Pu´ blica (CIBERESP)., JWJB: Verification of diabetes cases in EPIC-NL was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht., FLC: Cancer Research UK, PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart- Lung Foundation, JH: Danish Cancer Society, JMH: Health Research Fund of the Spanish Ministry of Health, Murcia Regional Government (Nu 6236), RK: German Cancer Aid, German Ministry of Research (BMBF), KTK: Medical Research Council UK, Cancer Research UK, PN: Swedish Research Council, KO: Danish Cancer Society, SP: Compagnia di San Paolo, JRQ: Asturias Regional Government, OR: The Vasterboten County Council, AT: Danish Cancer Society, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, ER: ER was supported in this work by the Imperial College Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, van den Berg, Sw, van der A., Dl, Spijkerman, Am, van Woudenbergh, Gj, Tijhuis, Mj, Amiano, P, Ardanaz, E, Beulens, Jw, Boeing, H, Clavel Chapelon, F, Crowe, Fl, de Lauzon Guillain, B, Fagherazzi, G, Franks, Pw, Freisling, H, Gonzalez, C, Grioni, S, Halkjaer, J, Huerta, Jm, Huybrechts, I, Kaaks, R, Khaw, Kt, Masala, G, Nilsson, Pm, Overvad, K, Panico, Salvatore, Quir?s, Jr, Rolandsson, O, Sacerdote, C, S?nchez, Mj, Schulze, Mb, Slimani, N, Struijk, Ea, Tjonneland, A, Tumino, R, Sharp, Sj, Langenberg, C, Forouhi, Ng, Feskens, Ej, Riboli, E, Wareham, Nj, and Interact, Consortium

Subjects
Gerontology, Anatomy and Physiology, endocrine system diseases, Nutrition and Disease, Epidemiology, lcsh:Medicine, Type 2 diabetes, Diabetes Mellitus Tipo 2, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Impaired glucose tolerance, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], MELLITUS, Endocrinology, Risk Factors, Voeding en Ziekte, Medicine and Health Sciences, Longitudinal Studies, lcsh:Science, Prospective cohort study, risk, METABOLIC SYNDROME, RISK, Multidisciplinary, Estudios de casos y controles, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], weight change, Ingestión de energía, WOMEN, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Energy Intake [Medical Subject Headings], Humanos, Europe, us adults, Endokrinologi och diabetes, Observational Studies, Medicine, Science & Technology - Other Topics, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], impaired glucose-tolerance, LIFE-STYLE, Dieta, women, Europa, Research Article, WEIGHT CHANGE, Factores de riesgo, life-style, Clinical Research Design, united-states, UNITED-STATES, Endocrine System, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Endocrinology and Diabetes, metabolic syndrome, IMPAIRED GLUCOSE-TOLERANCE, US ADULTS, Environmental health, Glycemic load, glycemic load, medicine, GLYCEMIC LOAD, Humans, Obesity, Biology, Nutrition, VLAG, Diabetic Endocrinology, Science & Technology, Population Biology, business.industry, MULTIDISCIPLINARY SCIENCES, lcsh:R, Weight change, Case-control study, Diabetes Mellitus Type 2, medicine.disease, Diet, Diabetes Mellitus, Type 2, Case-Control Studies, Other Clinical Medicine, lcsh:Q, Metabolic syndrome, Energy Intake, business, mellitus
Abstract

Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Observational studies implicate higher dietary energy density (DED) as a potential risk factor for weight gain and obesity. It has been hypothesized that DED may also be associated with risk of type 2 diabetes (T2D), but limited evidence exists. Therefore, we investigated the association between DED and risk of T2D in a large prospective study with heterogeneity of dietary intake. METHODOLOGY/PRINCIPAL FINDINGS A case-cohort study was nested within the European Prospective Investigation into Cancer (EPIC) study of 340,234 participants contributing 3.99 million person years of follow-up, identifying 12,403 incident diabetes cases and a random subcohort of 16,835 individuals from 8 European countries. DED was calculated as energy (kcal) from foods (except beverages) divided by the weight (gram) of foods estimated from dietary questionnaires. Prentice-weighted Cox proportional hazard regression models were fitted by country. Risk estimates were pooled by random effects meta-analysis and heterogeneity was evaluated. Estimated mean (sd) DED was 1.5 (0.3) kcal/g among cases and subcohort members, varying across countries (range 1.4-1.7 kcal/g). After adjustment for age, sex, smoking, physical activity, alcohol intake, energy intake from beverages and misreporting of dietary intake, no association was observed between DED and T2D (HR 1.02 (95% CI: 0.93-1.13), which was consistent across countries (I(2) = 2.9%). CONCLUSIONS/SIGNIFICANCE In this large European case-cohort study no association between DED of solid and semi-solid foods and risk of T2D was observed. However, despite the fact that there currently is no conclusive evidence for an association between DED and T2DM risk, choosing low energy dense foods should be promoted as they support current WHO recommendations to prevent chronic diseases. Yes

Published
2013
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8. Long-term risk of incident type 2 Diabetes and measures of overall and regional obesity: The EPIC-InterAct Case-Cohort Study

Author

Nicola D. Kerrison, Olov Rolandsson, Joachim Spranger, Nicholas J. Wareham, Kay-Tee Khaw, Luigi Palla, Carlos González, Heiner Boeing, Nita G. Forouhi, Ivonne Sluijs, María José Tormo, Joline W.J. Beulens, Kim Overvad, Matthias B. Schulze, Isabelle Romieu, Beverley Balkau, Francesca L. Crowe, Domenico Palli, María José Sánchez, J. Ramón Quirós, Claudia Langenberg, Yvonne T. van der Schouw, Dora Romaguera, Nadia Slimani, Paul W. Franks, Rosario Tumino, Eva Ardanaz, Göran Hallmans, Stephen J. Sharp, José María Huerta, Anne Tjønneland, Birgit Teucher, H. Bas Bueno-de-Mesquita, Salvatore Panico, Edith J. M. Feskens, Teresa Norat, L. van der A. Daphne, Carlotta Sacerdote, Elio Riboli, Annemieke M.W. Spijkerman, Blandine de Lauzon-Guillan, Peter M. Nilsson, Dagmar Drogan, Timothy J. Key, Sara Grioni, Rudolf Kaaks, Jytte Halkjær, Larraitz Arriola, Amalia Mattiello, Françoise Clavel-Chapelon, The InterAct Consortium, [Langenberg,C, Sharp,SJ, Forouhi,NG, Kerrison,ND, Palla,L, Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. [Schulze,MB] Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam Rehbruecke, Arthur-Scheunert-Allee, Nuthetal, Germany. [Rolandsson,O, Hallmans,G] Department of Public Health and Clinical Medicine, Umea University, Norrlands Universitetsjukhus, Umea, Sweden. [Overvad,K] Department of Epidemiology, School of Public Health, Aarhus C, Denmark. [Spranger.J] Charité-Universitatsmedizin Berlin, Department of Endocrinology, Diabetes and Nutrition, Berlin, Germany. [Drogan,D, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.[Arriola,L, Tormo,MJ] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Huerta,JM, Arriola,L, Tormo,MJ, Ardanaz,E, Sánchez,MJ] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pu´ blica), Madrid, Spain . [Arriola,L] Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain. Instituto BIO-Donostia, Hospital Donostia, Donostia, Basque Country. [Lauzon-Guillan,B, Balkau,B] INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018: Epidemiology of Diabetes, Obesity and Chronic Kidney Disease over the Lifecourse, Villejuif Cedex, France. University Paris, Villejuif Cedex, France. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Navarra, Spain. [Beulens,JWJ, Sluijs,I, Schouw,T] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Clavel-Chapelon,F] INSERM, CESP Centre for Research in Epidemiology and Population Health,U1018: Nutrition, Hormones and Women’s Health, IGR, Villejuif Cedex, France. [Crowe,FL, Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford,Richard Doll Building, Roosevelt Drive, Oxford, United Kingdom. [Grioni,S] Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy. [Halkjaer,J, Tjonneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Kerrison,ND, Teucher,B] German Cancer Research Centre, Heidelberg, Germany. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge Addenbrooke’s Hospital, Cambridge, United Kingdom. [Mattiello,A] Department of Clinical and Experimental Medicine Federico II University, Naples, Italy. [Nilsson,P, Panico,S] University of Lund, Department of Clinical Sciences Medicine, University Hospital Scania, Malmo, Sweden. [Norat,T, Romaguera,D, Riboli,E] Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. [Palli,D] Molecular and Nutritional Epidemiology Unit, ISPO Ponte Nuovo, Florence, Italy. [Quirós, JR] Public Health Directorate, Oviedo, Spain. [Romieu,I, Slimani,N] International Agency for Research on Cancer, Lyon Cedex, France. [Sacerdote,C] Center for Cancer Prevention (CPO-Piemonte), Torino, Italy. Human Genetics Foundation (HuGeF), Torino, Italy. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Spijkerman,AMW, A Daphne,L] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Tumino,R] Cancer Registry and Histopathology Unit, ‘‘Civile - M.P. Arezzo’’ Hospital, Dante Ragusa, Italy. [Feskens,EJM] Division of Human Nutrition - Section Nutrition and Epidemiology, University of Wageningen, Wageningen, The Netherlands. [Franks,PW] Department of Clinical Sciences, Clinical Research Center, Ska°ne University Hospital, Lund University, Malmö , Sweden. [Bueno-de-Mesquita,HB] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands., Funding: EU Integrated Project LSHM-CT-2006-037197. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. InterAct investigators acknowledge funding from the following agencies: KO: Danish Cancer Society, JS: ‘Heisenberg-Professorship (SP716/2-1), clinical research group (KFO218/1), and a research group (Molecular Nutrition to JS) support of the Bundesministerium fu¨ r Bildung und Forschung (BMBF), MJT: Health Research Fund (FIS) of the Spanish Ministry of Health, the CIBER en Epidemiologı´a y Salud Pu´ blica (CIBERESP), Spain, Murcia Regional Government (Nu 6236), JWJB, HBBdM, IS, AMWS, DLvdA, YTvdS: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, FLC: Cancer Research UK, PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation, GH: The county of Va¨sterbotten, RK: German Cancer Aid, Federal Ministry of Education and Research, TJK: Cancer Research UK, KK: Medical Research Council UK, Cancer Research UK, PN: Swedish Research Council, JRQ: Asturias Regional Government, BT: German Cancer Aid, Federal Ministry of Education and Research, AT: Danish Cancer Society, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government., Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, Langenberg, C, Sharp, Sj, Schulze, Mb, Rolandsson, O, Overvad, K, Forouhi, Ng, Spranger, J, Drogan, D, Huerta, Jm, Arriola, L, de Lauzon Guillan, B, Tormo, Mj, Ardanaz, E, Balkau, B, Beulens, Jw, Boeing, H, Bueno de Mesquita, Hb, Clavel Chapelon, F, Crowe, Fl, Franks, Pw, Gonzalez, Ca, Grioni, S, Halkjaer, J, Hallmans, G, Kaaks, R, Kerrison, Nd, Key, Tj, Khaw, Kt, Mattiello, A, Nilsson, P, Norat, T, Palla, L, Palli, D, Panico, Salvatore, Quir?s, Jr, Romaguera, D, Romieu, I, Sacerdote, C, S?nchez, Mj, Slimani, N, Sluijs, I, Spijkerman, Am, Teucher, B, Tjonneland, A, Tumino, R, van der A., Dl, van der Schouw, Yt, Feskens, Ej, Riboli, E, Wareham, Nj, and Interact, Consortium

Subjects
Male, Gerontology, Índice de Masa Corporal, Time Factors, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], Nutrition and Disease, Epidemiology, Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Anthropometry [Medical Subject Headings], body-mass index, Diabetes Mellitus Tipo 2, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Overweight, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Body Mass Index, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Endocrinology, prevention, Risk Factors, Voeding en Ziekte, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Waist Circumference [Medical Subject Headings], Cumulative incidence, Longitudinal Studies, Prospective Studies, Nutrition and Dietetics, Anthropometry, Incidence, primary-care, Hazard ratio, Absolute risk reduction, Geographicals::Geographic Locations::Europe [Medical Subject Headings], General Medicine, Middle Aged, waist circumference, Europe, Näringslära, nutrition, Cohort, Medicine, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], Female, medicine.symptom, Life Sciences & Biomedicine, Research Article, Cohort study, Clinical Research Design, abdominal adiposity, Check Tags::Male [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Endocrinology and Diabetes, Medicine, General & Internal, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], General & Internal Medicine, medicine, Humans, cancer, Obesity, Risk factor, Proportional Hazards Models, VLAG, Diabetic Endocrinology, Science & Technology, business.industry, association, nutritional and metabolic diseases, Diabetes Mellitus Type 2, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Diabetes Mellitus, Type 2, Antropometría, Check Tags::Female [Medical Subject Headings], Other Clinical Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Meta-Analyses, participants, business, Estudios de Cohortes, Body mass index, Demography, mellitus
Abstract

A collaborative re-analysis of data from the InterAct case-control study conducted by Claudia Langenberg and colleagues has established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index., Background Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI). Methods and Findings The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5–22.4 kg/m2) with a low WC (102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50–103 per 1,000 person-years in men and 28–74 per 1,000 person-years in women). Conclusions WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action. Please see later in the article for the Editors' Summary, Editors' Summary Background Worldwide, more than 350 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone that the pancreas releases after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. The long-term complications of diabetes, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes. Why Was This Study Done? A high body mass index (BMI, a measure of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is a strong predictor of type 2 diabetes. Although the risk of diabetes is greatest in obese people (who have a BMI of greater than 30 kg/m2), many of the people who develop diabetes are overweight—they have a BMI of 25–30 kg/m2. Healthy eating and exercise reduce the incidence of diabetes in high-risk individuals, but it is difficult and expensive to provide all overweight and obese people with individual lifestyle advice. Ideally, a way is needed to distinguish between people with high and low risk of developing diabetes at different levels of BMI. Waist circumference is a measure of fat distribution that has the potential to quantify diabetes risk among people with different BMIs because it estimates the amount of fat around the abdominal organs, which also predicts diabetes development. In this case-cohort study, the researchers use data from the InterAct study (which is investigating how genetics and lifestyle interact to affect diabetes risk) to estimate the long-term risk of type 2 diabetes associated with BMI and waist circumference. A case-cohort study measures exposure to potential risk factors in a group (cohort) of people and compares the occurrence of these risk factors in people who later develop the disease and in a randomly chosen subcohort. What Did the Researchers Do and Find? The researchers estimated the association of BMI and waist circumference with type 2 diabetes from baseline measurements of the weight, height, and waist circumference of 12,403 people who subsequently developed type 2 diabetes and a subcohort of 16,154 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC). Both risk factors were independently associated with type 2 diabetes risk, but waist circumference was a stronger risk factor in women than in men. Obese men (BMI greater than 35 kg/m2) with a high waist circumference (greater than 102 cm) were 22 times more likely to develop diabetes than men with a low normal weight (BMI 18.5–22.4 kg/m2) and a low waist circumference (less than 94 cm); obese women with a waist circumference of more than 88 cm were 31.8 times more likely to develop type 2 diabetes than women with a low normal weight and waist circumference (less than 80 cm). Importantly, among overweight people, waist circumference measurements identified a subgroup of overweight people (those with a high waist circumference) whose 10-year cumulative incidence of type 2 diabetes was similar to that of obese people. What Do These Findings Mean? These findings indicate that, among people of European descent, waist circumference is independently and strongly associated with type 2 diabetes, particularly among women. Additional studies are needed to confirm this association in other ethnic groups. Targeted measurement of waist circumference in overweight individuals (who now account for a third of the US and UK adult population) could be an effective strategy for the prevention of diabetes because it would allow the identification of a high-risk subgroup of people who might benefit from individualized lifestyle advice. Additional Information Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001230. The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health care professionals, and the general public, including detailed information on diabetes prevention (in English and Spanish) The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (including some information in Spanish) The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes, about the prevention of type 2 diabetes, and about obesity; it also includes peoples stories about diabetes and about obesity The charity Diabetes UK also provides detailed information for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the charity Healthtalkonline has interviews with people about their experiences of diabetes More information on the InterAct study is available MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention and about obesity (in English and Spanish)

Published
2012
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9. Tea consumption and incidence of type 2 diabetes in Europe: the EPIC-InterAct case-cohort study

Author

Birgit Teucher, Elio Riboli, Jytte Halkjær, Nita G. Forouhi, Françoise Clavel, Francesca L. Crowe, Joline W.J. Beulens, Kim Overvad, Edith J. M. Feskens, Dagmar Drogan, Geertruida J. van Woudenbergh, Giovanna Tagliabue, Kay-Tee Khaw, Matthias B. Schulze, Giovanna Masala, Ivonne Sluijs, Pilar Amiano, Heiner Boeing, Anne Tjønneland, M-Doleres Chirlaque, Peter M. Nilsson, Guy Fagherazzi, Olov Rolandsson, Nadia Slimani, Paul W. Franks, Claudia Langenberg, H. Bas Bueno-de-Mesquita, Annemieke M.W. Spijkerman, Daphne L. van der A, Nicholas J. Wareham, Christina C. Dahm, J. Ramón Quirós, Carlotta Sacerdote, Stephen J. Sharp, Eva Ardanaz, Isabelle Romieu, Dora Romaguera, Rosario Tumino, Amalia Mattiello, Aurelio Barricarte, Anneleen Kuijsten, Piia-Piret Eomois, María José Sánchez, InterAct Consortium, [van Woudenbergh, GJ, Kuijsten, A] Wageningen University, Division of Human Nutrition, Wageningen, The Netherlands. [Drogan, D, Boeing, H, Schulze, MB] German Institute of Human Nutrition Potsdam- Rehbruecke, Germany. [van der A, DL, Bueno-de-Mesquita, H. B, Spijkerman, AMW] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Romaguera, D, Riboli, E] Imperial College London, Department of Epidemiology & Biostatistics, School of Public Health, London, United Kingdom. [Ardanaz, E, Barricarte, A] Navarre Public Health Institute, Pamplona, Spain. [Amiano, P] Public Health Division of Gipuzkoa, San Sebastian, Spain. [Beulens, JWJ, Sluijs, I] University Medical Center, Utrecht, The Netherlands. [Dahm, CC., Overvad, K] School of Public Health, Aarhus University, Aarhus, Denmark. [Chirlaque, MD] Murcia Regional Health Authority, Spain . [Clavel, F, Fagher-azzi, G] Institut National de la Santé et de la Recherche Médicale (INSERM) and Center for Research in Epidemiology and Population Health (CESP), France. [Crowe, FL] University of Oxford, Oxford, United Kingdom. [Eomois, P, Teucher, B] German Cancer Research Center, Heidelberg, Germany. [Franks, PW] Lund University, Malmo, Sweden. [Halkjaer, J, Tjonneland, A] Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Khaw, KT] University of Cambridge, Cambridge, United Kingdom. [Masala, G] Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Mattiello, A] Federico II University, Naples, Italy. [Quiros, JR] Asturias Health & Health Care Council, Oviedo, Spain. [Rolandsson, O] Department of Public Health and Clinical Medicine, Family Medicine, Umea University, Umea , Sweden. [Romieu, I] International Agency for Research of Cancer, Lyon, France. [Sacerdote, C] Center for Cancer Prevention, Torino, Italy. [Sanchez, MJ] Andalusian School of Public Health, Granada, Spain. [Tagliabue, G] Cancer Registry and Environmental Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino, R] Cancer Registry and Histopathology Unit, Ragusa, Italy. [Forouhi, NG, Sharp, S, Langenberg, C, Wareham, NJ] MRC Epidemiology Unit, Cambridge, United Kingdom., The EPIC-InterAct project was funded by the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Program 6 of the European Community). In addition, EPIC-InterAct investigators acknowledge funding from the following agencies:-DLvdA, AMWS, and HBBdM: Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), EA and AB: Health Research Fund (FIS), Regional Governments of Andalucı´a, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), JWJB and IS: Verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, AM: Compagnia di San Paolo, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (Nu 6236), and CIBER Epidemiologı´a y Salud Pu´ blica (CIBERESP), Spain, FC: Cancer Research UK, AT, JH, CCD, and KO: Danish Cancer Society, OR: Va¨sterbotten County Council, PWF: Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation, JRQ: Regional Government of the Principality of Asturias (Spain), PN and LG: Swedish Research Council, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, KTK: Medical Research Council UK, Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, and APH - Health Behaviors & Chronic Diseases

Subjects
Male, obesity, Anatomy and Physiology, Non-Clinical Medicine, Nutrition and Disease, black tea, Epidemiology, lcsh:Medicine, Type 2 diabetes, Diabetes Mellitus Tipo 2, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Cohort Studies, Dinámicas no Lineales, Endocrinology, Mediana Edad, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior [Medical Subject Headings], Surveys and Questionnaires, Voeding en Ziekte, oolong tea, Té, Cuestionarios, lcsh:Science, Masculino, Chemicals and Drugs::Complex Mixtures::Biological Agents::Plant Preparations::Tea [Medical Subject Headings], risk, milk, Multidisciplinary, Adulto, Incidence (epidemiology), Hazard ratio, Femenino, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], food and beverages, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Adulto Joven, Middle Aged, Humanos, Europe, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Cohort, Endokrinologi och diabetes, Medicine, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], Female, Europa, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Nonlinear Dynamics [Medical Subject Headings], Cohort study, Research Article, metaanalysis, Adult, medicine.medical_specialty, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Clinical Research Design, green tea, Anciano, coffee, Drinking Behavior, Endocrine System, Health Informatics, Endocrinology and Diabetes, Lower risk, complex mixtures, Riesgo, Young Adult, Diabetes mellitus, Conducta de Ingestión de Líquido, medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, cancer, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Cardiovascular Disease Epidemiology, plasma, Aged, VLAG, Diabetic Endocrinology, Tea, business.industry, lcsh:R, Diabetes Mellitus Type 2, medicine.disease, Obesity, Surgery, Diabetes Mellitus, Type 2, Nonlinear Dynamics, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], lcsh:Q, business, Estudios de Cohortes, Demography
Abstract

Background: In previous meta-analyses, tea consumption has been associated with lower incidence of type 2 diabetes. It is unclear, however, if tea is associated inversely over the entire range of intake. Therefore, we investigated the association between tea consumption and incidence of type 2 diabetes in a European population. Methodology/Principal Findings: The EPIC-InterAct case-cohort study was conducted in 26 centers in 8 European countries and consists of a total of 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,835 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Country-specific Hazard Ratios (HR) for incidence of type 2 diabetes were obtained after adjustment for lifestyle and dietary factors using a Cox regression adapted for a case-cohort design. Subsequently, country-specific HR were combined using a random effects meta-analysis. Tea consumption was studied as categorical variable (0, >0

Published
2012
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