Author: "Huerta, José María" / Topic: middle aged - Searchworks@Jio Institute Digital Library Search Results

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1. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Author: Molina‐Montes, Esther, Sánchez, María‐José, Zamora‐Ros, Raul, Bueno‐de‐Mesquita, HB, Wark, Petra A, Obon‐Santacana, Mireia, Kühn, Tilman, Katzke, Verena, Travis, Ruth C, Ye, Weimin, Sund, Malin, Naccarati, Alessio, Mattiello, Amalia, Krogh, Vittorio, Martorana, Caterina, Masala, Giovanna, Amiano, Pilar, Huerta, José‐María, Barricarte, Aurelio, Quirós, José‐Ramón, Weiderpass, Elisabete, Åsli, Lene Angell, Skeie, Guri, Ericson, Ulrika, Sonestedt, Emily, Peeters, Petra H, Romieu, Isabelle, Scalbert, Augustin, Overvad, Kim, Clemens, Matthias, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Vidalis, Pavlos, Khaw, Kay‐Tee, Wareham, Nick, Olsen, Anja, Tjønneland, Anne, Boutroun‐Rualt, Marie‐Christine, Clavel‐Chapelon, Françoise, Cross, Amanda J, Lu, Yunxia, Riboli, Elio, and Duell, Eric J
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Digestive Diseases, Nutrition, Pancreatic Cancer, Rare Diseases, Complementary and Integrative Health, Cancer, Prevention, Cohort Studies, Diet, Diet Records, Europe, Female, Flavonoids, Humans, Life Style, Lignans, Male, Middle Aged, Pancreatic Neoplasms, Proportional Hazards Models, Prospective Studies, cohort, diet, flavonoids, lignans, pancreatic cancer, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow-up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center-stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable-adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95-1.11 and 1.02; 95% CI: 0.89-1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91-1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.
Published: 2016

2. Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Zamora-Ros, Raul, Knaze, Viktoria, Rothwell, Joseph A, Hémon, Bertrand, Moskal, Aurelie, Overvad, Kim, Tjønneland, Anne, Kyrø, Cecilie, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Touillaud, Marina, Katzke, Verena, Kühn, Tilman, Boeing, Heiner, Förster, Jana, Trichopoulou, Antonia, Valanou, Elissavet, Peppa, Eleni, Palli, Domenico, Agnoli, Claudia, Ricceri, Fulvio, Tumino, Rosario, de Magistris, Maria Santucci, Peeters, Petra HM, Bueno-de-Mesquita, H Bas, Engeset, Dagrun, Skeie, Guri, Hjartåker, Anette, Menéndez, Virginia, Agudo, Antonio, Molina-Montes, Esther, Huerta, José María, Barricarte, Aurelio, Amiano, Pilar, Sonestedt, Emily, Nilsson, Lena Maria, Landberg, Rikard, Key, Timothy J, Khaw, Kay-Thee, Wareham, Nicholas J, Lu, Yunxia, Slimani, Nadia, Romieu, Isabelle, Riboli, Elio, and Scalbert, Augustin
Subjects: Public Health, Biomedical and Clinical Sciences, Nutrition and Dietetics, Health Sciences, Complementary and Integrative Health, Nutrition, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Cancer, Adult, Aged, Body Mass Index, Coffee, Cross-Sectional Studies, Diet, Europe, Exercise, Female, Flavonoids, Food Analysis, Food Handling, Fruit, Humans, Hydroxybenzoates, Life Style, Male, Mental Recall, Middle Aged, Nutrition Assessment, Polyphenols, Proanthocyanidins, Prospective Studies, Socioeconomic Factors, Tea, Dietary intake, EPIC, Food sources, Nutrition & Dietetics, Nutrition and dietetics, Epidemiology
Abstract: Background/objectivesPolyphenols are plant secondary metabolites with a large variability in their chemical structure and dietary occurrence that have been associated with some protective effects against several chronic diseases. To date, limited data exist on intake of polyphenols in populations. The current cross-sectional analysis aimed at estimating dietary intakes of all currently known individual polyphenols and total intake per class and subclass, and to identify their main food sources in the European Prospective Investigation into Cancer and Nutrition cohort.MethodsDietary data at baseline were collected using a standardized 24-h dietary recall software administered to 36,037 adult subjects. Dietary data were linked with Phenol-Explorer, a database with data on 502 individual polyphenols in 452 foods and data on polyphenol losses due to cooking and food processing.ResultsMean total polyphenol intake was the highest in Aarhus-Denmark (1786 mg/day in men and 1626 mg/day in women) and the lowest in Greece (744 mg/day in men and 584 mg/day in women). When dividing the subjects into three regions, the highest intake of total polyphenols was observed in the UK health-conscious group, followed by non-Mediterranean (non-MED) and MED countries. The main polyphenol contributors were phenolic acids (52.5-56.9 %), except in men from MED countries and in the UK health-conscious group where they were flavonoids (49.1-61.7 %). Coffee, tea, and fruits were the most important food sources of total polyphenols. A total of 437 different individual polyphenols were consumed, including 94 consumed at a level >1 mg/day. The most abundant ones were the caffeoylquinic acids and the proanthocyanidin oligomers and polymers.ConclusionThis study describes the large number of dietary individual polyphenols consumed and the high variability of their intakes between European populations, particularly between MED and non-MED countries.
Published: 2016

3. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study

Author: Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Peeters, Petra H., Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J., Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay Tee, Wareham, Nick, Bradbury, Kathryn E., Perez-Cornago, Aurora, Tsilidis, Konstantinos K., Ferrari, Pietro, Riboli, Elio, Gunter, Marc J., Touvier, Mathilde, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris 13 (UP13)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition and Metabolism Section, International Agency for Research on Cancer, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Cancer Registry of Norway, Institute of Population-Based Cancer Research, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Public Health, Section for Epidemiology, Aarhus University [Aarhus], Danish Cancer Society Research Center, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), 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)-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), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, German Institute of Human Nutrition (DIfE), WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Cancer registry and histopathology unit, Civile - M.P.Arezzo Hospital, Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital-Center for Cancer Prevention (CPO-Piemonte), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], School of Public Health - Department of Epidemiology and Biostatistics, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Julius Center for Health Sciences and Primary Care, Department of Nutrition [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Public Health Directorate Asturias, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, L´Hospitallet de Llobregat, Facultat de Ciències de la Salut Blanquerna, Universitat Ramon Llull [Barcelona] (URL), Escuela Andaluza de Salud Publica, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Public Health Institute of Navarra, IdiSNA, Navarra Institute for Health Research, Public Health Department of Gipuzkoa, Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences, Clinical Research Center, Lund University [Lund]-Lund University [Lund], Nutritional Epidemiology, Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy, University of Gothenburg (GU), Department of Odontology, Umeå University, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, Institute of Metabolic Science, Nuffield Department of Population Health - Cancer Epidemiology Unit, University of Oxford [Oxford], Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, French National Cancer Institute (INCa)-Canceropole Ile-de-France [2017-1-PL SHS-01-INSERM ADR 5-1], European Commission (DG-SANCO), Danish Cancer Society (Denmark), Ligue Contre le Cancer, (France), Institut Gustave Roussy, (France), Mutuelle Generale de l'Education Nationale, (France), Institut National de la Sante et de la Recherche Medicale (Inserm), (France), Deutsche Krebshilfe (Germany), Deutsches Krebsforschungszentrum (Germany), Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Dutch Ministry of Public Health, Welfare, and Sports (VWS) (the Netherlands), Netherlands Cancer Registry (NKR) (the Netherlands), LK Research Funds (the Netherlands), Dutch Prevention Funds (the Netherlands), Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands), World Cancer Research Fund (WCRF) (the Netherlands), Statistics Netherlands (the Netherlands), Health Research Fund (FIS) [PI13/00061], Regional Government of Andalucia (Spain), Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) [6236], Regional Government of Navarra, ISCIII RETIC (Spain) [RD06/0020], Swedish Cancer Society (Sweden), Swedish Scientific Council (Sweden), County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK [14136, C570/A16491, C8221/A19170], Medical Research Council [1000143, MR/M012190/1], National Research Council (Italy), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Hôpital avicenne, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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)-Institut Gustave Roussy (IGR), 'CIVIC-M.P. AREZZO' Hospital, University of Oxford, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR), Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Deschasaux, Mélanie [0000-0002-3359-420X], Huybrechts, Inge [0000-0003-3838-855X], Murphy, Neil [0000-0003-3347-8249], Hercberg, Serge [0000-0002-3168-1350], Srour, Bernard [0000-0002-1277-3380], Kesse-Guyot, Emmanuelle [0000-0002-9715-3534], Weiderpass, Elisabete [0000-0003-2237-0128], Dahm, Christina C [0000-0003-0481-2893], Kyrø, Cecilie [0000-0002-9083-8960], Olsen, Anja [0000-0003-4788-503X], Boutron-Ruault, Marie-Christine [0000-0002-5956-5693], Mahamat-Saleh, Yahya [0000-0002-5892-8886], Tumino, Rosario [0000-0003-2666-414X], Sacerdote, Carlotta [0000-0002-8008-5096], Hjartåker, Anette [0000-0003-3002-4030], Skeie, Guri [0000-0003-2476-4251], Jakszyn, Paula [0000-0003-0672-8847], Huerta, José María [0000-0002-9637-3869], Sonestedt, Emily [0000-0002-0747-4562], Johansson, Ingegerd [0000-0002-9227-8434], Wareham, Nick [0000-0003-1422-2993], Bradbury, Kathryn E [0000-0003-3345-7333], Perez-Cornago, Aurora [0000-0002-5652-356X], Riboli, Elio [0000-0001-6795-6080], Touvier, Mathilde [0000-0002-8322-8857], Apollo - University of Cambridge Repository, Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C, Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Luka, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-de-Mesquita, Ba, Peeters, Petra H, Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J, Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Perez-Cornago, Aurora, Tsilidis, Konstantinos K, Ferrari, Pietro, Riboli, Elio, Gunter, Marc J, and Touvier, Mathilde
Subjects: Adult, Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nutrition Policy, Cohort Studies, Food Preferences, Medicine, General & Internal, project, Food Labeling, Risk Factors, front-of-package, su.vi.max cohort, General & Internal Medicine, Neoplasms, Humans, french adults, Prospective Studies, dietary index, database, Medicine(all), validation, Nutrition and Dietetics, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, 11 Medical And Health Sciences, Middle Aged, Näringslära, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Europe, prospective association, 3121 General medicine, internal medicine and other clinical medicine, Medicine, Female, cardiovascular-disease risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Life Sciences & Biomedicine, Nutritive Value, france, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Source at https://doi.org/10.1371/journal.pmed.1002651. Background - Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. Methods and findings - This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992–2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03–1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions - In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
Published: 2018

4. Prospective evaluation of antibody response to Streptococcus gallolyticus and risk of colorectal cancer

Author: Butt, Julia, Jenab, Mazda, Willhauck-Fleckenstein, Martina, Michel, Angelika, Pawlita, Michael, Kyrø, Cecilie, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Severi, Gianluca, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Trichopoulou, Antonia, la Vecchia, Carlo, Karakatsani, Anna, Panico, Salvatore, Tumino, Rosario, Agnoli, Claudia, Palli, Domenico, Sacerdote, Carlotta, Bueno-de-Mesquita, H B As, Weiderpass, Elisabete, Sánchez, Maria-José, Bonet Bonet, Catalina, Huerta, José María, Ardanaz, Eva, Bradbury, Kathryn, Gunter, Marc, Murphy, Neil, Freisling, Heinz, Riboli, Elio, Tsilidis, Kostas, Aune, Dagfinn, Waterboer, Tim, Hughes, David J, Butt, Julia, Jenab, Mazda, Willhauck-Fleckenstein, Martina, Michel, Angelika, Pawlita, Michael, Kyrø, Cecilie, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Severi, Gianluca, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Trichopoulou, Antonia, la Vecchia, Carlo, Karakatsani, Anna, Panico, Salvatore, Tumino, Rosario, Agnoli, Claudia, Palli, Domenico, Sacerdote, Carlotta, Bueno-de-Mesquita, H B A, Weiderpass, Elisabete, Sánchez, Maria-José, Bonet Bonet, Catalina, Huerta, José María, Ardanaz, Eva, Bradbury, Kathryn, Gunter, Marc, Murphy, Neil, Freisling, Heinz, Riboli, Elio, Tsilidis, Kosta, Aune, Dagfinn, Waterboer, Tim, and Hughes, David J
Subjects: Adult, Male, prospective cohort, Middle Aged, Antibodies, Bacterial, Gastrointestinal Microbiome, Streptococcus gallolyticu, antibodie, Bacterial Proteins, Case-Control Studies, Streptococcal Infections, bacterial serology, Odds Ratio, Humans, Female, Prospective Studies, colorectal neoplasm, Colorectal Neoplasms, Streptococcus gallolyticus subspecies gallolyticus, Aged
Abstract: The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to eleven SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the eleven SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study we observed a positive association between antibody responses to SGG and CRC development in serum samples taken pre-diagnostically. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification. This article is protected by copyright. All rights reserved.
Published: 2018

5. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease:A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort

Author: Key, Timothy J, Appleby, Paul N, Bradbury, Kathryn E, Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Würtz, Anne Mette Lund, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M A, Bonnet, Fabrice, Boutron-Ruault, Marie-Christine, Cross, Amanda J, Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay-Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Verschuren, W M Monique, Di Angelantonio, Emanuele, Langenberg, Claudia, Forouhi, Nita, Wareham, Nick, Butterworth, Adam, Riboli, Elio, and Danesh, John
Subjects: Male, Adult, VASCULAR MORTALITY, Eggs/adverse effects, Time Factors, Myocardial Ischemia/blood, BLOOD-PRESSURE, Blood Pressure, Meat/adverse effects, Recommended Dietary Allowances, Diet Surveys, Risk Assessment, Europe/epidemiology, meat, Risk Factors, eggs, Humans, Prospective Studies, Aged, fish, CALIBRATION, INDIVIDUAL DATA, Cholesterol, HDL/blood, heart diseases, dairy products, CHOLESTEROL, food and beverages, UPDATED METAANALYSIS, ASSOCIATION, Middle Aged, Protective Factors, CANCER, Cross-Sectional Studies, RED MEAT, Seafood/adverse effects, LIFE-STYLE, Female, Diet, Healthy, Dairy Products/adverse effects, Nutritive Value, Risk Reduction Behavior, Biomarkers/blood
Abstract: Background: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). Methods: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. Results: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. Conclusions: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.
Published: 2019

6. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease

Author: Key, Timothy J, Appleby, Paul N, Bradbury, Kathryn E, Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Lund Würtz, Anne Mette, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M A, Bonnet, Fabrice, Boutron-Ruault, Marie-Christine, Cross, Amanda J, Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay-Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Verschuren, W M Monique, di Angelantonio, Emanuele, Langenberg, Claudia, Forouhi, Nita, Wareham, Nick, Butterworth, Adam, Riboli, Elio, Danesh, John, Wood, Angela [0000-0002-7937-304X], Steur, Marina [0000-0002-9028-0290], Di Angelantonio, Emanuele [0000-0001-8776-6719], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita [0000-0002-5041-248X], Wareham, Nicholas [0000-0003-1422-2993], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
Subjects: Adult, Male, Meat, Time Factors, Eggs, Myocardial Ischemia, Blood Pressure, Recommended Dietary Allowances, Diet Surveys, Risk Assessment, Risk Factors, Original Research Articles, Humans, Prospective Studies, Aged, fish, heart diseases, dairy products, Cholesterol, HDL, Middle Aged, Protective Factors, Europe, Cross-Sectional Studies, eggs, meat, Seafood, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Diet, Healthy, Nutritive Value, Risk Reduction Behavior, Biomarkers
Abstract: Supplemental Digital Content is available in the text., Background: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). Methods: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. Results: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06–1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09–1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89–0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86–0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88–0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non–high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non–high-density lipoprotein cholesterol. Conclusions: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non–high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.
Published: 2019

7. Anthropometry and the Risk of Lung Cancer in EPIC

Author: Dewi, Nikmah Utami, Boshuizen, Hendriek C, Johansson, Mattias, Vineis, Paolo, Kampman, Ellen, Steffen, Annika, Tjønneland, Anne, Halkjær, Jytte, Overvad, Kim, Severi, Gianluca, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Kaaks, Rudolf, Li, Kuanrong, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Klinaki, Eleni, Tumino, Rosario, Palli, Domenico, Mattiello, Amalia, Tagliabue, Giovanna, Peeters, Petra H, Vermeulen, Roel, Weiderpass, Elisabete, Torhild Gram, Inger, Huerta, José María, Agudo, Antonio, Sánchez, María-José, Ardanaz, Eva, Dorronsoro, Miren, Quirós, José Ramón, Sonestedt, Emily, Johansson, Mikael, Grankvist, Kjell, Key, Tim, Khaw, Kay-Tee, Wareham, Nick, Cross, Amanda J, Norat, Teresa, Riboli, Elio, Fanidi, Anouar, Muller, David, Bueno-de-Mesquita, H Bas, LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, and Imperial College Trust
Subjects: Male, obesity, Lung Neoplasms, Nutrition and Disease, Epidemiology, Comorbidity, waist to hip ratio, ORIGINAL CONTRIBUTIONS, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 0302 clinical medicine, Waist–hip ratio, Voeding en Ziekte, Multicenter Studies as Topic, Medicine, Prospective Studies, 030212 general & internal medicine, POPULATION, Public, Environmental & Occupational Health, Human Nutrition & Health, Waist-to-height ratio, Anthropometry, Hazard ratio, Humane Voeding & Gezondheid, Confounding Factors, Epidemiologic, 11 Medical And Health Sciences, Middle Aged, waist circumference, Europe, LEANNESS, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Waist, body mass index, waist-to-height ratio, Risk Assessment, smoking, 03 medical and health sciences, Journal Article, Humans, COHORT, Lung cancer, waist-to-heigh ratio, METAANALYSIS, 01 Mathematical Sciences, Aged, Proportional Hazards Models, VLAG, MODEL ANALYSIS, Science & Technology, Waist-Hip Ratio, business.industry, Proportional hazards model, CURRENT SMOKERS, Cancer, FAT DISTRIBUTION, medicine.disease, Diet, Surgery, BODY-MASS INDEX, lung cancer, business, Body mass index, Demography
Abstract: The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.
Published: 2016

8. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women : the European Prospective Investigation into Cancer and Nutrition Study (EPIC)

Author: Ekelund, Ulf, Ward, Heather A, Norat, Teresa, Luan, Jian'An, May, Anne M, Weiderpass, Elisabete, Sharp, Stephen J, Overvad, Kim, Østergaard, Jane Nautrup, Tjønneland, Anne, Johnsen, Nina Føns, Mesrine, Sylvie, Fournier, Agnès, Fagherazzi, Guy, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Li, Kuanrong, Kaaks, Rudolf, Ferrari, Pietro, Licaj, Idlir, Jenab, Mazda, Bergmann, Manuela, Boeing, Heiner, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Peeters, Petra H, Monnikhof, Evelyn, Bueno de Mesquita, H. Bas, Quirós, J. Ramón, Agudo, Antonio, Sánchez, María José, Huerta, José María, Ardanaz, Eva, Arriola, Larraitz, Hedblad, Bo, Wirfält, Elisabet, Sund, Malin, Johansson, Mattias, Key, Timothy J, Travis, Ruth C, Khaw, Kay Tee, Brage, Søren, Wareham, Nicholas J, Riboli, Elio, PANICO, SALVATORE, Imperial College Trust, Luan, Jian'an [0000-0003-3137-6337], Sharp, Stephen [0000-0003-2375-1440], Khaw, Kay-Tee [0000-0002-8802-2903], Brage, Soren [0000-0002-1265-7355], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Ekelund, Ulf, Ward, Heather A, Norat, Teresa, Luan, Jian'An, May, Anne M, Weiderpass, Elisabete, Sharp, Stephen J, Overvad, Kim, Østergaard, Jane Nautrup, Tjønneland, Anne, Johnsen, Nina Føn, Mesrine, Sylvie, Fournier, Agnè, Fagherazzi, Guy, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Li, Kuanrong, Kaaks, Rudolf, Ferrari, Pietro, Licaj, Idlir, Jenab, Mazda, Bergmann, Manuela, Boeing, Heiner, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Peeters, Petra H, Monnikhof, Evelyn, Bueno de Mesquita, H. Ba, Quirós, J. Ramón, Agudo, Antonio, Sánchez, María José, Huerta, José María, Ardanaz, Eva, Arriola, Larraitz, Hedblad, Bo, Wirfält, Elisabet, Sund, Malin, Johansson, Mattia, Key, Timothy J, Travis, Ruth C, Khaw, Kay Tee, Brage, Søren, Wareham, Nicholas J, and Riboli, Elio
Subjects: Male, obesity, physical activity, 09 Engineering, Body Mass Index, Cohort Studies, Hospitals, University, Risk Factors, PARTICIPANTS, LIFE EXPECTANCY, Prospective Studies, Adiposity, RISK, Sex Characteristics, Nutrition and Dietetics, exercise, Public Health, Global Health, Social Medicine and Epidemiology, 11 Medical And Health Sciences, Middle Aged, Europe, population attributable action, Näringslära, CARDIOVASCULAR-DISEASE, Obesity, Abdominal, Female, epidemiology, HEALTH, Waist Circumference, COLLEGE, Life Sciences & Biomedicine, Human, Adult, COUNTRIES, Outpatient Clinics, Hospital, Abdominal Fat, QUESTIONNAIRE, Motor Activity, Follow-Up Studie, cohort study, Humans, VALIDITY, Proportional Hazards Models, Science & Technology, Nutrition & Dietetics, Risk Factor, Sex Characteristic, mortality, Prospective Studie, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Proportional Hazards Model, Self Report, Cohort Studie, population attributable fraction, Follow-Up Studies
Abstract: BACKGROUND: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear.OBJECTIVE: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures.DESIGN: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures.RESULTS: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity.CONCLUSION: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
Published: 2015

9. Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Author: Molina-Montes, Esther, Sánchez, María José, Zamora-Ros, Raul, Bueno-de-Mesquita, H. Bas, Wark, Petra A., Obon-Santacana, Mireia, Kühn, Tilman, Katzke, Verena, Travis, Ruth C., Ye, Weimin, Sund, Malin, Naccarati, Alessio, Mattiello, Amalia, Krogh, Vittorio, Martorana, Caterina, Masala, Giovanna, Amiano, Pilar, Huerta, José María, Barricarte, Aurelio, Quirós, José Ramón, Weiderpass, Elisabete, Angell Åsli, Lene, Skeie, Guri, Ericson, Ulrika, Sonestedt, Emily, Peeters, Petra H., Romieu, Isabelle, Scalbert, Augustin, Overvad, Kim, Clemens, Matthias, Boeing, Heiner, Trichopoulou, Antonia, Peppa, Eleni, Vidalis, Pavlos, Khaw, Kay Tee, Wareham, Nick, Olsen, Anja, Tjønneland, Anne, Boutroun-Rualt, Marie Christine, Clavel-Chapelon, Françoise, Cross, Amanda J., Lu, Yunxia, Riboli, Elio, Duell, Eric J., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Male, Cancer Research, Oncology and Carcinogenesis, pancreatic cancer, Cohort Studies, Rare Diseases, Complementary and Integrative Health, Journal Article, Humans, Oncology & Carcinogenesis, Prospective Studies, Life Style, Nutrition, Cancer, Proportional Hazards Models, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Prevention, lignans, food and beverages, cohort, Middle Aged, Diet Records, Europe, Pancreatic Neoplasms, Multicenter Study, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Oncology, flavonoids, Female, Digestive Diseases, diet, Cancer Epidemiology
Abstract: Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort., What's new? Flavonoids and lignans found in plant‐based foods are potent cancer chemopreventive agents but little is known about their effects on pancreatic cancer risk. Here the authors address this question in a large prospective epidemiological study using comprehensively derived dietary data. Their results support growing evidence that there is no association between food‐based consumption of both substances with pancreatic cancer risk.
Published: 2016

10. Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Engeset, Dagrun, Braaten, Tonje, Teucher, Birgit, Kühn, Tilman, Bueno-de-Mesquita, H. B., Leenders, Max, Agudo, Antonio, Bergmann, Manuela M., Valanou, Elisavet, Naska, Androniki, Trichopoulou, Antonia, Key, Timothy J., Crowe, Francesca L., Overvad, Kim, Sonestedt, Emily, Mattiello, Amalia, Peeters, Petra H., Wennberg, Maria, Jansson, Jan Håkan, Boutron-Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Li, Kuanrong, Barricarte, Aurelio, Ward, Heather, Riboli, Elio, Agnoli, Claudia, Huerta, José María, Sánchez, María José, Tumino, Rosario, Altzibar, Jone M., Vineis, Paolo, Masala, Giovanna, Ferrari, Pietro, Muller, David C., Johansson, Mattias, Luisa Redondo, M., Tjønneland, Anne, Olsen, Anja, Olsen, Karina Standahl, Brustad, Magritt, Skeie, Guri, Lund, Eiliv, Infection & Immunity, Risk Assessment, dIRAS RA-I&I RA, LS IRAS EEPI GRA (Gezh.risico-analyse), Infection & Immunity, Risk Assessment, dIRAS RA-I&I RA, and LS IRAS EEPI GRA (Gezh.risico-analyse)
Subjects: Male, Questionnaires, Epidemiology, Myocardial Ischemia, Risk Factors, Neoplasms, Surveys and Questionnaires, Nutritional Epidemiology, CONTAMINANTS, Prospective Studies, Prospective cohort study, Public, Environmental & Occupational Health, RISK, CALIBRATION, MEAT, Incidence (epidemiology), Incidence, Hazard ratio, Fishes, Cohort, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, VDP::811, Multi-centre study, 1117 Public Health And Health Services, VDP::771, Lean fish, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Fatty fish, MODELS, Fish consumption, Nutritional Status, DIETARY, VDP::762, Environmental health, Fatty Acids, Omega-3, medicine, Animals, Humans, CORONARY-HEART-DISEASE, Mortality, METAANALYSIS, Aged, Proportional Hazards Models, Science & Technology, business.industry, Proportional hazards model, DANISH ADULTS, Confidence interval, Diet, Seafood, business, FISHERMEN
Abstract: Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992–1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99 % confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p
Published: 2015

11. Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer

Author: Kyrø, Cecilie, Olsen, Anja, Landberg, Rikard, Skeie, Guri, Loft, Steffen, Åman, Per, Leenders, Max, Dik, Vincent K., Siersema, Peter D., Pischon, Tobias, Christensen, Jane, Overvad, Kim, Boutron-Ruault, Marie Christine, Fagherazzi, Guy, Cottet, Vanessa, Kühn, Tilman, Chang-Claude, Jenny, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Trichopoulos, Dimitrios, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Peeters, Petra H., Weiderpass, Elisabete, Bakken, Toril, Åsli, Lene Angell, Argüelles, Marcial, Jakszyn, Paula, Sánchez, María José, Amiano, Pilar, Huerta, José María, Barricarte, Aurelio, Ljuslinder, Ingrid, Palmqvist, Richard, Khaw, Kay Tee, Wareham, Nick, Key, Timothy J., Travis, Ruth C., Ferrari, Pietro, Freisling, Heinz, Jenab, Mazda, Gunter, Marc J., Murphy, Neil, Riboli, Eilo, Tjønneland, Anne, Bueno-De-Mesquita, H. B., LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, Risk Assessment of Toxic and Immunomodulatory Agents, Kyr?, C, Olsen, A, Landberg, R, Skeie, G, Loft, S, Aman, P, Leenders, M, Dik, Vk, Siersema, Pd, Pischon, T, Christensen, J, Overvad, K, Boutron Ruault, Mc, Fagherazzi, G, Cottet, V, K?hn, T, Chang Claude, J, Boeing, H, Trichopoulou, A, Bamia, C, Trichopoulos, D, Palli, D, Krogh, V, Tumino, R, Vineis, P, Panico, Salvatore, Peeters, Ph, Weiderpass, E, Bakken, T, Asli, La, Arg?elles, M, Jakszyn, P, S?nchez, Mj, Amiano, P, Huerta, Jm, Barricarte, A, Ljuslinder, I, Palmqvist, R, Khaw, Kt, Wareham, N, Key, Tj, Travis, Rc, Ferrari, P, Freisling, H, Jenab, M, Gunter, Mj, Murphy, N, Riboli, E, Tj?nneland, A, Bueno de Mesquita, Hb, LS IRAS EEPI GRA (Gezh.risico-analyse), IRAS RATIA-SIB, and Risk Assessment of Toxic and Immunomodulatory Agents
Subjects: Male, medicine.medical_specialty, Pathology, Cancer Research, Colorectal cancer, Scandinavian and Nordic Countries, Rate ratio, Gastroenterology, Body Mass Index, Alkylresorcinol, Risk Factors, Internal medicine, Odds Ratio, Medicine, Humans, Triticum, Aged, Cancer och onkologi, business.industry, Mediterranean Region, Incidence (epidemiology), Incidence, Secale, Case-control study, food and beverages, Cancer, Odds ratio, Feeding Behavior, Resorcinols, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Logistic Models, Oncology, Cardiovascular and Metabolic Diseases, Cancer and Oncology, Case-Control Studies, Female, business, Colorectal Neoplasms, Biomarkers
Abstract: Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.
Published: 2013

12. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron-Ruault, Marie-Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina EN, Overvad, Kim, Quirós, J Ramón, Jakszyn, Paula, Molina-Montes, Esther, Dorronsoro, Miren, Huerta, José-María, Barricarte, Aurelio, Khaw, Kay-Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno-De-Mesquita, H Bas, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kostas, Muller, David C, Riboli, Elio, and Gunter, Marc J
Subjects: Male, Health Status, Risk Assessment, Body Mass Index, Risk Factors, Hyperinsulinism, Odds Ratio, Body Size, Humans, Obesity, Prospective Studies, Adiposity, 2. Zero hunger, Obesity, Metabolically Benign, Chi-Square Distribution, C-Peptide, Incidence, nutritional and metabolic diseases, Middle Aged, Protective Factors, 3. Good health, Europe, Logistic Models, Phenotype, Case-Control Studies, Multivariate Analysis, Female, Waist Circumference, Colorectal Neoplasms, Biomarkers
Abstract: BACKGROUND: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of

13. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease

Author: Key, Timothy J, Appleby, Paul N, Bradbury, Kathryn E, Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Lund Würtz, Anne Mette, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda MA, Bonnet, Fabrice, Boutron-Ruault, Marie-Christine, Cross, Amanda J, Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay-Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, Van Der Schouw, Yvonne T, Verschuren, WM Monique, Di Angelantonio, Emanuele, Langenberg, Claudia, Forouhi, Nita, Wareham, Nick, Butterworth, Adam, Riboli, Elio, and Danesh, John
Subjects: Adult, Male, Meat, Time Factors, Eggs, Myocardial Ischemia, Blood Pressure, Recommended Dietary Allowances, Diet Surveys, Risk Assessment, Risk Factors, Humans, Prospective Studies, Aged, 2. Zero hunger, fish, heart diseases, dairy products, Cholesterol, HDL, food and beverages, Middle Aged, Protective Factors, 3. Good health, Europe, Cross-Sectional Studies, Seafood, Female, Diet, Healthy, Nutritive Value, Risk Reduction Behavior, Biomarkers
Abstract: BACKGROUND: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). METHODS: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.

14. Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study

Author: Zheng, Ju-Sheng, Sharp, Stephen J, Imamura, Fumiaki, Koulman, Albert, Schulze, Matthias B, Ye, Zheng, Griffin, Jules, Guevara, Marcela, Huerta, José María, Kröger, Janine, Sluijs, Ivonne, Agudo, Antonio, Barricarte, Aurelio, Boeing, Heiner, Colorado-Yohar, Sandra, Dow, Courtney, Dorronsoro, Miren, Dinesen, Pia T, Fagherazzi, Guy, Franks, Paul W, Feskens, Edith JM, Kühn, Tilman, Katzke, Verena Andrea, Key, Timothy J, Khaw, Kay-Tee, De Magistris, Maria Santucci, Mancini, Francesca Romana, Molina-Portillo, Elena, Nilsson, Peter M, Olsen, Anja, Overvad, Kim, Palli, Domenico, Quirós, Jose Ramón, Rolandsson, Olov, Ricceri, Fulvio, Spijkerman, Annemieke MW, Slimani, Nadia, Tagliabue, Giovanna, Tjonneland, Anne, Tumino, Rosario, Van Der Schouw, Yvonne T, Langenberg, Claudia, Riboli, Elio, Forouhi, Nita G, and Wareham, Nicholas J
Subjects: Adult, Blood Glucose, Male, Body Mass Index, Young Adult, Hepatic, Humans, Saturated fatty acids, Prospective Studies, Triglycerides, Aged, 2. Zero hunger, Inflammation, Cholesterol, HDL, Fatty Acids, Cholesterol, LDL, Middle Aged, Lipids, Dietary Fats, 3. Good health, Europe, Metabolic markers, Cross-Sectional Studies, Even-chain, lipids (amino acids, peptides, and proteins), Female, Very-long-chain, Glycaemic, Odd-chain, Biomarkers
Abstract: BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. RESULTS: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. CONCLUSIONS: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

15. Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

Author: Fedirko, Veronika, Jenab, Mazda, Méplan, Catherine, Jones, Jeb S, Zhu, Wanzhe, Schomburg, Lutz, Siddiq, Afshan, Hybsier, Sandra, Overvad, Kim, Tjønneland, Anne, Omichessan, Hanane, Perduca, Vittorio, Boutron-Ruault, Marie-Christine, Kühn, Tilman, Katzke, Verena, Aleksandrova, Krasimira, Trichopoulou, Antonia, Karakatsani, Anna, Kotanidou, Anastasia, Tumino, Rosario, Panico, Salvatore, Masala, Giovanna, Agnoli, Claudia, Naccarati, Alessio, Bueno-De-Mesquita, Bas, Vermeulen, Roel CH, Weiderpass, Elisabete, Skeie, Guri, Nøst, Therese Haugdahl, Lujan-Barroso, Leila, Quirós, J Ramón, Huerta, José María, Rodríguez-Barranco, Miguel, Barricarte, Aurelio, Gylling, Björn, Harlid, Sophia, Bradbury, Kathryn E, Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc, Murphy, Neil, Freisling, Heinz, Tsilidis, Kostas, Aune, Dagfinn, Riboli, Elio, Hesketh, John E, and Hughes, David J
Subjects: Adult, Male, genetic epidemiology, Genotype, selenoprotein P, prospective cohort, Nutritional Status, selenoprotein gene variation, Polymorphism, Single Nucleotide, Cohort Studies, Selenium, Humans, Genetic Predisposition to Disease, Prospective Studies, Selenoproteins, Aged, integumentary system, colorectal cancer risk, biomarkers, colorectal neoplasms, Middle Aged, 3. Good health, selenium pathway, Gene Expression Regulation, selenium status, Female
Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

16. Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study

Author: Deschasaux, Mélanie, Huybrechts, Inge, Murphy, Neil, Julia, Chantal, Hercberg, Serge, Srour, Bernard, Kesse-Guyot, Emmanuelle, Latino-Martel, Paule, Biessy, Carine, Casagrande, Corinne, Jenab, Mazda, Ward, Heather, Weiderpass, Elisabete, Dahm, Christina C, Overvad, Kim, Kyrø, Cecilie, Olsen, Anja, Affret, Aurélie, Boutron-Ruault, Marie-Christine, Mahamat-Saleh, Yahya, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Schwingshackl, Lukas, Bamia, Christina, Peppa, Eleni, Trichopoulou, Antonia, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Bueno-De-Mesquita, Bas, Peeters, Petra H, Hjartåker, Anette, Rylander, Charlotta, Skeie, Guri, Ramón Quirós, J, Jakszyn, Paula, Salamanca-Fernández, Elena, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Sonestedt, Emily, Huseinovic, Ena, Johansson, Ingegerd, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Perez-Cornago, Aurora, Tsilidis, Konstantinos K, Ferrari, Pietro, Riboli, Elio, Gunter, Marc J, and Touvier, Mathilde
Subjects: 2. Zero hunger, Adult, Male, Middle Aged, 3. Good health, Nutrition Policy, Cohort Studies, Europe, Food Preferences, Food Labeling, Risk Factors, Neoplasms, Humans, Female, Prospective Studies, Nutritive Value
Abstract: BACKGROUND: Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. METHODS AND FINDINGS: This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. CONCLUSIONS: In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.

17. Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Author: Stepien, Magdalena, Hughes, David J, Hybsier, Sandra, Bamia, Christina, Tjønneland, Anne, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron-Ruault, Marie-Christine, Katzke, Verena, Kühn, Tilman, Aleksandrova, Krasimira, Trichopoulou, Antonia, Lagiou, Pagona, Orfanos, Phlippos, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-De-Mesquita, HB As, Peeters, Petra H, Weiderpass, Elisabete, Lasheras, Cristina, Bonet Bonet, Catalina, Molina-Portillo, Elena, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Ohlsson, Bodil, Sjöberg, Klas, Werner, Mårten, Shungin, Dmitry, Wareham, Nick, Khaw, Kay-Tee, Travis, Ruth C, Freisling, Heinz, Cross, Amanda J, Schomburg, Lutz, and Jenab, Mazda
Subjects: Male, Carcinoma, Hepatocellular, Liver Neoplasms, Middle Aged, 3. Good health, Europe, Zinc, Biliary Tract Neoplasms, Case-Control Studies, Humans, Female, Prospective Studies, Copper, Aged
Abstract: BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed. CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

18. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author: Zheng, Ju-Sheng, Luan, Jian'an, Sofianopoulou, Eleni, Sharp, Stephen J, Day, Felix R, Imamura, Fumiaki, Gundersen, Thomas E, Lotta, Luca A, Sluijs, Ivonne, Stewart, Isobel D, Shah, Rupal L, Van Der Schouw, Yvonne T, Wheeler, Eleanor, Ardanaz, Eva, Boeing, Heiner, Dorronsoro, Miren, Dahm, Christina C, Dimou, Niki, El-Fatouhi, Douae, Franks, Paul W, Fagherazzi, Guy, Grioni, Sara, Huerta, José María, Heath, Alicia K, Hansen, Louise, Jenab, Mazda, Jakszyn, Paula, Kaaks, Rudolf, Kühn, Tilman, Khaw, Kay-Tee, Laouali, Nasser, Masala, Giovanna, Nilsson, Peter M, Overvad, Kim, Olsen, Anja, Panico, Salvatore, Quirós, J Ramón, Rolandsson, Olov, Rodríguez-Barranco, Miguel, Sacerdote, Carlotta, Spijkerman, Annemieke MW, Tong, Tammy YN, Tumino, Rosario, Tsilidis, Konstantinos K, Danesh, John, Riboli, Elio, Butterworth, Adam S, Langenberg, Claudia, Forouhi, Nita G, and Wareham, Nicholas J
Subjects: Adult, Male, Mendelian Randomization Analysis, Middle Aged, White People, 3. Good health, Diabetes Mellitus, Type 2, Risk Factors, Dietary Supplements, Humans, Female, Prospective Studies, Vitamin D, Genome-Wide Association Study
Abstract: BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

19. Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort

Author: Sarink, Danja, Schock, Helena, Johnson, Theron, Chang-Claude, Jenny, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Arveux, Patrick, Fournier, Agnès, Kvaskoff, Marina, Boeing, Heiner, Karakatsani, Anna, Trichopoulou, Antonia, La Vecchia, Carlo, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Van Gils, Carla H, Peeters, Petra HM, Weiderpass, Elisabete, Agudo, Antonio, Rodríguez-Barranco, Miguel, Huerta, José María, Ardanaz, Eva, Gil, Leire, Kaw, Kay Tee, Schmidt, Julie A, Dossus, Laure, His, Mathilde, Aune, Dagfinn, Riboli, Elio, Kaaks, Rudolf, and Fortner, Renée T
Subjects: musculoskeletal diseases, Adult, Risk, Epidemiology, RANK Ligand, Osteoprotegerin, Breast Neoplasms, Middle Aged, Prognosis, 3. Good health, Cohort Studies, Breast cancer, Limit of Detection, Case-Control Studies, Humans, Female, Reproductive, hormonal, and related factors, Serum biomarkers of endogenous exposures, Aged
Abstract: BACKGROUND: Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis. METHODS: Two thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models. RESULTS: Especially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis. CONCLUSIONS: High pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.

20. Association of plasma phospholipid n-3 and n-6 polyunsaturated fatty acids with type 2 diabetes: The EPIC-InterAct case-cohort study

Author: Forouhi, N, Imamura, F, Sharp, S, Koulman, A, Schulze, M, Zheng, J, Ye, Z, Sluijs, I, Guevara, M, Huerta, J, Kröger, J, Wang, L, Summerhill, K, Griffin, J, Feskens, E, Affret, A, Amiano, P, Boeing, H, Dow, C, Fagherazzi, G, Franks, P, Gonzalez, C, Kaaks, R, Key, T, Khaw, K, Kühn, T, Mortensen, L, Nilsson, P, Overvad, K, Pala, V, Palli, D, Panico, S, Quirós, J, Rodriguez-Barranco, M, Rolandsson, O, Sacerdote, C, Scalbert, A, Slimani, N, Spijkerman, A, Tjonneland, A, Tormo, M, Tumino, R, van der A, D, van der Schouw, Y, Langenberg, C, Riboli, E, Wareham, N, Forouhi, Nita G, Imamura, Fumiaki, Sharp, Stephen J, Koulman, Albert, Schulze, Matthias B, Zheng, Jusheng, Ye, Zheng, Sluijs, Ivonne, Guevara, Marcela, Huerta, José María, Kröger, Janine, Wang, Laura Yun, Summerhill, Keith, Griffin, Julian L, Feskens, Edith J. M, Affret, Aurélie, Amiano, Pilar, Boeing, Heiner, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Gonzalez, Carlo, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Kühn, Tilman, Mortensen, Lotte Maxild, Nilsson, Peter M, Overvad, Kim, Pala, Valeria, Palli, Domenico, Panico, Salvatore, Quirós, J. Ramón, Rodriguez Barranco, Miguel, Rolandsson, Olov, Sacerdote, Carlotta, Scalbert, Augustin, Slimani, Nadia, Spijkerman, Annemieke M. W, Tjonneland, Anne, Tormo, Maria Jose, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Langenberg, Claudia, Riboli, Elio, Wareham, Nicholas J., Apollo - University of Cambridge Repository, [Forouhi,NG, Imamura,F, Sharp,SJ, Zheng,J, Ye,Z, Langenberg,C, Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. [Koulman,A, Wang,LY, Summerhill,K, Griffin,JL] MRC Human Nutrition Research, Cambridge, UK. [Schulze,MB, Kröger,J, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. [Sluijs,I, van der Schouw,YT] University Medical Center Utrecht, Utrecht, the Netherlands. [Guevara,M] Navarre Public Health Institute (ISPN), Pamplona, Spain. [Guevara,M, Huerta,JM, Amiano,P, Rodriguez-Barranco,M, Tormo,M] CIBER Epidemiología y Salud Pública (CIBERESP), Spain. [Huerta,M, Tormo,M] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Feskens,EJM] Wageningen University, The Netherlands. [Affret,A, Dow,C, Fagherazzi,G] Inserm, CESP, U1018, Villejuif, France. Univ Paris-Sud, Villejuif, France, Gustave Roussy Institute, Villejuif, France. [Amiano,P] Public Health Division of Gipuzkoa, San Sebastian, Spain. Instituto BIO-Donostia, Basque Government, San Sebastian, Spain. [Boeing,H] German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. [Franks,PW, Nilsson,PM] Lund University, Malmö, Sweden. [Franks,PW, Rolandsson,O] Umeå University, Umeå, Sweden. [Gonzalez,C] Catalan Institute of Oncology (ICO), Barcelona, Spain. [Kaaks,R, Kühn1,T] German Cancer Research Centre (DKFZ), Heidelberg, Germany. [Key1,TJ] University of Oxford, Oxford, United Kingdom. [Khaw,KT] University of Cambridge, Cambridge, United Kingdom. [Mortensen,M] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Mortensen,M, Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Overvad,K] Aalborg University Hospital, Aalborg, Denmark. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Palli,D] Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Rodriguez-Barranco,M] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sacerdote,C] Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy. Human Genetics Foundation (HuGeF), Turin, Italy. [Scalbert,A, Slimani,N] International Agency for Research on Cancer, Lyon, France. [Spijkerman,AMW, van der A,DL] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Tjonneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tormo,MJ] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Tumino,R] Cancer Registry and Histopathology Unit, Civic and M.P.Arezzo Hospital, ASP Ragusa, Italy. [Riboli,E] School of Public Health, Imperial College London, London, United Kingdom., Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197)., Imamura, Fumiaki [0000-0002-6841-8396], Sharp, Stephen J [0000-0003-2375-1440], Koulman, Albert [0000-0001-9998-051X], Sluijs, Ivonne [0000-0001-7758-4911], Guevara, Marcela [0000-0001-9242-6364], Huerta, José María [0000-0002-9637-3869], Rodriguez-Barranco, Miguel [0000-0002-9972-9779], Tormo, Maria-Jose [0000-0003-1474-5233], van der Schouw, Yvonne T [0000-0002-4605-435X], Langenberg, Claudia [0000-0002-5017-7344], and Wareham, Nicholas J [0000-0003-1422-2993]
Subjects: Male, Physiology, Social Sciences, Diabetes Mellitus Tipo 2, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6::Linoleic Acids [Medical Subject Headings], Anatomy::Fluids and Secretions::Body Fluids::Blood::Plasma [Medical Subject Headings], Biochemistry, Plasma, Mathematical and Statistical Techniques, Endocrinology, Sociology, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings], Plant Products, Estudios prospectivos, Medicine and Health Sciences, Fosfolípidos, Ácidos grasos omega 3, Phospholipids, Medicine(all), Schools, Fatty Acids, Geographicals::Geographic Locations::Europe [Medical Subject Headings], food and beverages, Agriculture, Ácido eicosapentaenoico, 11 Medical And Health Sciences, Hematology, Middle Aged, Lipids, Type 2 Diabetes, Body Fluids, Blood, Ácidos Grasos Omega-6, Ácido 8,11,14-eicosanoico, Endokrinologi och diabetes, Physical Sciences, Fatty Acids, Unsaturated, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings], Medicine, Dieta, lipids (amino acids, peptides, and proteins), Anatomy, Europa, Statistics (Mathematics), Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids [Medical Subject Headings], Research Article, Cromatografía de gases, 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], Endocrine Disorders, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Eicosanoids::8,11,14-Eicosatrienoic Acid [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Endocrinology and Diabetes, Research and Analysis Methods, Vegetable Oils, Blood Plasma, Education, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Docosahexaenoic Acids [Medical Subject Headings], General & Internal Medicine, Fatty Acids, Omega-6, Fatty Acids, Omega-3, Ácidos docosahexaenoicos, Diabetes Mellitus, Journal Article, Humans, Statistical Methods, Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings], Ácido araquidónico, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Chromatography::Chromatography, Gas [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6 [Medical Subject Headings], Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Eicosapentaenoic Acid [Medical Subject Headings], Ácidos Grasos Insaturados, Biology and Life Sciences, Ácido linoleico, Agronomy, Diabetes Mellitus, Type 2, Metabolic Disorders, Case-Control Studies, Oils, Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated [Medical Subject Headings], Mathematics, Meta-Analysis, Crop Science
Abstract: Background Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations. Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88–0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77–0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85–0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs. Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class., Using a large European cohort, Nita Forouhi and colleagues investigate the association between the concentration of polyunsaturated fatty acids measured in plasma and risk of developing type 2 diabetes., Author Summary Why Was This Study Done? Most dietary guidelines recommend the consumption of polyunsaturated fatty acids for cardiovascular health, but it is unclear whether or how n-3 and n-6 types of polyunsaturated fatty acids are related to type 2 diabetes. Health concerns have been raised previously about a diet high in linoleic acid (n-6 fatty acid), but its association with type 2 diabetes is unclear. Major limitations in previous studies have included the error-prone subjective assessment of the habitual consumption of polyunsaturated fatty acids when dietary intakes were evaluated and a small number of type 2 diabetes cases (n = 71 to 673) when objective biomarkers of polyunsaturated fatty acids were measured. What Did the Researchers Do and Find? We measured circulating individual polyunsaturated fatty acids in the blood samples of individuals within a large study from across eight countries of Europe among a reference sample of 15,919 individuals as well as 12,132 individuals who subsequently developed diabetes. Individuals were followed up for an average of approximately 10 y. We investigated the association between individual polyunsaturated fatty acids and the risk of future type 2 diabetes using statistical analyses that accounted for factors that could be potential alternative explanations for any observed associations. We found that higher levels of blood alpha-linolenic acid, a plant-origin n-3 fatty acid, and n-6 linoleic acid, the most abundant type of polyunsaturated fatty acid, were associated with a lower risk of future type 2 diabetes. In contrast, higher levels of four other minor individual n-6 fatty acids were associated with higher type 2 diabetes risk, while the blood marine-origin n-3 fatty acids were not associated with future diabetes. What Do These Findings Mean? Our findings show that it is important to consider individual circulating polyunsaturated fatty acids for association with type 2 diabetes risk, rather than placing emphasis on the class of circulating polyunsaturated fatty acids. We found that blood n-6 linoleic acid, the most abundant polyunsaturated fatty acid, is inversely associated with type 2 diabetes. We found no evidence that blood total n-6 polyunsaturated fatty acids may elevate the risk of type 2 diabetes, but several individual minor blood n-6 polyunsaturated fatty acids were associated with increased type 2 diabetes risk, highlighting the importance of polyunsaturated fatty acid metabolism in the development of type 2 diabetes.
Published: 2016
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21. The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Author: Nita G. Forouhi, Kim Overvad, Ivonne Sluijs, Tammy Y.N. Tong, Christina C. Dahm, Kay-Tee Khaw, Thomas E. Gundersen, José María Huerta, Peter M. Nilsson, Miguel Rodríguez-Barranco, Nasser Laouali, Adam S. Butterworth, Giovanna Masala, Sara Grioni, Rosario Tumino, Anja Olsen, Stephen J. Sharp, Salvatore Panico, J. Ramón Quirós, Yvonne T. van der Schouw, Eleanor Wheeler, Rudolf Kaaks, Alicia K Heath, Eva Ardanaz, Felix R. Day, Eleni Sofianopoulou, Konstantinos K. Tsilidis, Luca A. Lotta, Nicholas J. Wareham, Douae El-Fatouhi, Claudia Langenberg, Heiner Boeing, Guy Fagherazzi, Paula Jakszyn, Olov Rolandsson, Rupal L. Shah, Mazda Jenab, Miren Dorronsoro, Ju-Sheng Zheng, Fumiaki Imamura, Isobel D. Stewart, Elio Riboli, Paul W. Franks, Louise Hansen, John Danesh, Carlotta Sacerdote, Jian'an Luan, Niki Dimou, Annemieke M.W. Spijkerman, Tilman Kühn, Zheng, Ju-Sheng [0000-0001-6560-4890], Sharp, Stephen J [0000-0003-2375-1440], Day, Felix R [0000-0003-3789-7651], Sluijs, Ivonne [0000-0001-7758-4911], Shah, Rupal L [0000-0001-8789-8869], van der Schouw, Yvonne T [0000-0002-4605-435X], Dahm, Christina C [0000-0003-0481-2893], Dimou, Niki [0000-0003-1678-9328], Franks, Paul W [0000-0002-0520-7604], Fagherazzi, Guy [0000-0001-5033-5966], Huerta, José María [0000-0002-9637-3869], Heath, Alicia K [0000-0001-6517-1300], Hansen, Louise [0000-0002-7109-8864], Jenab, Mazda [0000-0002-0573-1852], Kühn, Tilman [0000-0001-7702-317X], Laouali, Nasser [0000-0002-8532-456X], Masala, Giovanna [0000-0002-5758-9069], Olsen, Anja [0000-0003-4788-503X], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Sacerdote, Carlotta [0000-0002-8008-5096], Tong, Tammy YN [0000-0002-0284-8959], Tumino, Rosario [0000-0003-2666-414X], Tsilidis, Konstantinos K [0000-0002-8452-8472], Riboli, Elio [0000-0001-6795-6080], Langenberg, Claudia [0000-0002-5017-7344], Forouhi, Nita G [0000-0002-5041-248X], Wareham, Nicholas J [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Sharp, Stephen J. [0000-0003-2375-1440], Day, Felix R. [0000-0003-3789-7651], Shah, Rupal L. [0000-0001-8789-8869], van der Schouw, Yvonne T. [0000-0002-4605-435X], Dahm, Christina C. [0000-0003-0481-2893], Franks, Paul W. [0000-0002-0520-7604], Heath, Alicia K. [0000-0001-6517-1300], Tong, Tammy Y. N. [0000-0002-0284-8959], Tsilidis, Konstantinos K. [0000-0002-8452-8472], Forouhi, Nita G. [0000-0002-5041-248X], and Wareham, Nicholas J. [0000-0003-1422-2993]
Subjects: Male, Single Nucleotide Polymorphisms, Organic chemistry, Genome-wide association study, Type 2 diabetes, VARIANTS, 030204 cardiovascular system & hematology, Biochemistry, Endocrinology, Medical Conditions, Mathematical and Statistical Techniques, 0302 clinical medicine, DESIGN, Risk Factors, Medicine and Health Sciences, Metabolites, VITAMIN-D SUPPLEMENTATION, 030212 general & internal medicine, Prospective Studies, Vitamin D, 11 Medical and Health Sciences, RISK, Diabetis, Statistics, Diabetes, Genomics, Vitamins, General Medicine, Metaanalysis, Middle Aged, Type 2 Diabetes, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Physical sciences, Chemistry, OBESITY, Endokrinologi och diabetes, Medicine, LIFE-STYLE, Female, Life Sciences & Biomedicine, Research Article, Adult, medicine.medical_specialty, Endocrine Disorders, DATABASE, Vitamina D, European Continental Ancestry Group, Single-nucleotide polymorphism, Endocrinology and Diabetes, Research and Analysis Methods, Lower risk, White People, Chemical compounds, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Internal medicine, Organic compounds, Diabetes Mellitus, Genome-Wide Association Studies, medicine, Vitamin D and neurology, Genetics, Humans, Statistical Methods, Science & Technology, business.industry, Biology and Life Sciences, Computational Biology, Human Genetics, Odds ratio, Mendelian Randomization Analysis, Genome Analysis, medicine.disease, Metabolism, Diabetes Mellitus, Type 2, Genetic Loci, Metabolic Disorders, Relative risk, Dietary Supplements, GENETIC-DETERMINANTS, business, Mathematics, Genètica, Genome-Wide Association Study
Abstract: Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. Methods and findings We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]–InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1–standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. Conclusions Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D., Using both observational and genetic analyses, Ju-Sheng Zheng and colleagues investigate the relationship between vitamin D metabolites and type 2 diabetes among European individuals., Author summary Why was this study done? There is ongoing uncertainty on whether the body’s vitamin D status indicated by blood 25-hydroxyvitamin D (25(OH)D) is relevant to the prevention of type 2 diabetes. There are conflicting findings from observational studies and a limited number of randomised controlled trials. Prior research did not distinguish between different metabolites of total 25(OH)D, including 25(OH)D3 and C3-epi-25(OH)D3, an isomer of 25(OH)D3. It is not clear whether the associations of 25(OH)D metabolites with type 2 diabetes are causal, with conflicting findings from prior Mendelian randomisation studies of total 25(OH)D and no previous Mendelian randomisation studies appraising 25(OH)D metabolites. What did the researchers do and find? The current research compared observational estimates of the association between 25(OH)D metabolites and incident type 2 diabetes with Mendelian randomisation estimates based on genetic instruments. Using multiple data sources, we performed genome-wide association studies among 120,618 individuals for total 25(OH)D, and among 40,562 individuals for the other vitamin D metabolites. Among participants of European descent, 10 genetic loci were identified for total 25(OH)D, 7 loci for 25(OH)D3 and 3 loci for C3-epi-25(OH)D3. In meta-analysis of observational studies, we found that each 1–standard deviation higher level of total 25(OH)D was associated with 20% lower risk of type 2 diabetes. The result was similar for 25(OH)D3, but for C3-epi-25(OH)D3, a positive association with type 2 diabetes was found. With up to 80,983 type 2 diabetes cases and 842,909 controls, we assessed the association of genetically predicted differences in total 25(OH)D and its metabolites with type 2 diabetes. Neither genetically predicted higher total 25(OH)D level nor genetically predicted higher levels of 25(OH)D metabolites were significantly associated with type 2 diabetes. What do these findings mean? There were conflicting findings for a link with type 2 diabetes for the observational analysis of biochemically measured 25(OH)D metabolites versus the genetically predicted levels of these metabolites. The null findings based on Mendelian randomisation analysis indicate that blood levels of 25(OH)D or its metabolites are not likely to be causal factors for the development of type 2 diabetes. The current findings together with other evidence from randomised controlled trials do not support the use of vitamin D supplementation for the prevention of type 2 diabetes.
Published: 2020

22. Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis

Author: Sara Grioni, Giuseppe Matullo, Heiner Boeing, Ioanna Tzoulaki, J. Ramón Quirós, Yvonne T. van der Schouw, Concepción Moreno-Iribas, Jolanda M. A. Boer, Elio Riboli, Michail Katsoulis, Larraitz Arriola, Guri Skeie, Pietro Ferrari, Emanuele Di Angelantonio, Timothy J. Key, Adam S. Butterworth, Matthias Johansson, Gunnar Engström, Antonia Trichopoulou, Patrik Wennberg, Verena Katzke, Fabrice Bonnet, Calogero Saieva, Elisabete Weiderpass, Heinz Freisling, W M Monique Verschuren, Anne Kirstine Eriksen, Laura Johnson, Annika Steffen, Kim Overvad, John Danesh, Karel G.M. Moons, Magdalena Stepien, Margareta Norberg, Michael J. Sweeting, Vassiliki Benetou, Nicholas J. Wareham, Olle Melander, Elena Molina-Portillo, Claudia Agnoli, Rudolf Kaaks, Camille Lassale, Salvatore Panico, Claudia Langenberg, Rosario Tumino, Anne Tjønneland, José María Huerta, Sandra Colorado-Yohar, Daphne L. van der A, Lassale, Camille, Tzoulaki, Ioanna, Moons, Karel G. M, Sweeting, Michael, Boer, Jolanda, Johnson, Laura, Huerta, José María, Agnoli, Claudia, Freisling, Heinz, Weiderpass, Elisabete, Wennberg, Patrik, Van Der A, Daphne L, Arriola, Larraitz, Benetou, Vassiliki, Boeing, Heiner, Bonnet, Fabrice, Colorado yohar, Sandra M, Engström, Gunnar, Eriksen, Anne K, Ferrari, Pietro, Grioni, Sara, Johansson, Matthia, Kaaks, Rudolf, Katsoulis, Michail, Katzke, Verena, Key, Timothy J, Matullo, Giuseppe, Melander, Olle, Molina portillo, Elena, Moreno iribas, Concepción, Norberg, Margareta, Overvad, Kim, Panico, Salvatore, Quirós, J. Ramón, Saieva, Calogero, Skeie, Guri, Steffen, Annika, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Van Der Schouw, Yvonne T, Verschuren, W. M. Monique, Langenberg, Claudia, Di Angelantonio, Emanuele, Riboli, Elio, Wareham, Nicholas J, Danesh, John, Butterworth, Adam S., Imperial College Trust, and Commission of the European Communities
Subjects: Gerontology, Male, obesity, Cardiac & Cardiovascular Systems, Epidemiology, CARDIOMETABOLIC TRAITS, physical activity, Coronary Disease, 030204 cardiovascular system & hematology, Body Mass Index, German, 0302 clinical medicine, 030212 general & internal medicine, ALL-CAUSE MORTALITY, media_common, Adiposity, 2. Zero hunger, Coronary heart disease, Metabolic syndrome, Obesity, METABOLICALLY HEALTHY, Middle Aged, waist circumference, 3. Good health, Europe, MENDELIAN RANDOMIZATION, language, Female, body mass index procedure, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Cohort study, medicine.medical_specialty, 1102 Cardiovascular Medicine And Haematology, smoking, POOLED ANALYSIS, 03 medical and health sciences, medicine, Journal Article, media_common.cataloged_instance, Humans, overweight, European union, coronary heart disease, Metabolic health, INCIDENT CARDIOVASCULAR-DISEASE, Government, Science & Technology, business.industry, FAT DISTRIBUTION, coronary heart disease risk, medicine.disease, language.human_language, BODY-MASS INDEX, PHYSICAL-ACTIVITY, Cardiovascular System & Hematology, Family medicine, Case-Control Studies, Cardiovascular System & Cardiology, RISK-FACTORS, business
Abstract: Aims: The hypothesis of ‘metabolically healthy obesity’ implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study. Methods and results: We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study (‘EPIC-CVD’). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction (‘unhealthy’) as >_ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses. Conclusion: Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of ‘metabolically healthy obesity’, encouraging population-wide strategies to tackle obesity., European Union (EU) HEALTH-F2-2012-279233, European Research Council (ERC) 268834, Medical Research Council UK (MRC) G0800270 MR/L003120/1 MR/M012190/1, British Heart Foundation SP/09/002 RG/08/014 RG13/13/30194, National Institute for Health Research (NIHR), Regional Government of Asturias, Hellenic Health Foundation, German Cancer Aid, German Cancer Research Centre, German Federal Ministry of Education and Research, Cancer Research UK 570/A16491, Regione Sicilia, Associazione Iblea per la Ricerca Epidemiologica (A.I.R.E.) - ONLUS Ragusa, Associazione Volontari Italiani Sangue AVIS Ragusa, Compagnia di San Paolo, Human Genetics Foundation-Torino (HuGeF), British Heart Foundation RG/13/13/30194 RG/08/014/24067, Cancer Research UK 16491, Medical Research Council UK (MRC) MR/L003120/1 G0800270 MC_UU_12015/1, National Institute for Health Research (NIHR) NF-SI-0512-10135 NF-SI-0512-10165, Novo Nordisk Foundation NNF17OC0026936
Published: 2019

23. Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status

Author: Krasimira Aleksandrova, Leila Lujan-Barroso, Kim Overvad, Marc J. Gunter, Jeb Jones, Anna Karakatsani, Giovanna Masala, J. Ramón Quirós, John E. Hesketh, José María Huerta, Sophia Harlid, Aurelio Barricarte, Salvatore Panico, Anastasia Kotanidou, Kostas Tsilidis, Afshan Siddiq, Bas Bueno-de-Mesquita, Dagfinn Aune, Tilman Kühn, Therese Haugdahl Nøst, Guri Skeie, Mazda Jenab, Kay-Tee Khaw, Catherine Méplan, Marie-Christine Boutron-Ruault, Elio Riboli, Hanane Omichessan, Rosario Tumino, Antonia Trichopoulou, Wanzhe Zhu, Heinz Freisling, Claudia Agnoli, Nicholas J. Wareham, Alessio Naccarati, Kathryn E. Bradbury, Miguel Rodríguez-Barranco, Neil Murphy, Verena Katzke, Elisabete Weiderpass, Veronika Fedirko, Björn Gylling, Vittorio Perduca, Roel Vermeulen, Sandra Hybsier, Anne Tjønneland, David J. Hughes, Lutz Schomburg, Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, International Agency for Cancer Research (IACR), Experimental Endocrinology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Imperial College London, Department of Clinical Epidemiology, Aarhus University Hospital, Institute of Cancer Epidemiology, Danish Cancer Society, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Molecular and Nutritional Epidemiology Unit (ISPO), Cancer Research and Prevention Institute, Fondazione IRCCS Istituto Nazionale dei Tumori, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Community Medicine, University of Tromsø (UiT), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, MRC epidemiology Unit, Addenbrooke's Hospital, Clinical Gerontology Unit, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, University of Oxford [Oxford], Department of Epidemiology and Biostatistics, School of Cellular and Molecular Biosciences, Newcastle University [Newcastle], Charite Medical School Berlin, Aalborg Hospital-Aarhus University Hospital, Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 'Civile M.P.Arezzo' hospital, Jones, Jeb S [0000-0001-9165-1658], Schomburg, Lutz [0000-0001-9445-1555], Perduca, Vittorio [0000-0003-0339-0473], Tumino, Rosario [0000-0003-2666-414X], Agnoli, Claudia [0000-0003-4472-1179], Weiderpass, Elisabete [0000-0003-2237-0128], Skeie, Guri [0000-0003-2476-4251], Lujan-Barroso, Leila [0000-0001-6224-1764], Huerta, José María [0000-0002-9637-3869], Rodríguez-Barranco, Miguel [0000-0002-9972-9779], Gylling, Björn [0000-0002-4688-8952], Harlid, Sophia [0000-0001-8540-6891], Freisling, Heinz [0000-0001-8648-4998], Hughes, David J [0000-0003-1668-8770], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Colorectal cancer, selenoprotein P, SUSCEPTIBILITY, Selenoprotein gene variation, Cohort Studies, Epidemiologia genètica, 0302 clinical medicine, GENETIC-VARIANTS, Genetic epidemiology, Prospective Studies, Selenoproteins, selenium, ComputingMilieux_MISCELLANEOUS, Genetics, chemistry.chemical_classification, ARCHITECTURE, Nutrition and Dietetics, integumentary system, Selenoprotein P, Middle Aged, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710, CROHNS-DISEASE, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Näringslära, selenium pathway, 030220 oncology & carcinogenesis, selenium status, Female, HEALTH, Selenium status, 3143 Nutrition, Life Sciences & Biomedicine, lcsh:Nutrition. Foods and food supply, FRIZZLED-RELATED PROTEIN, Adult, MEGALIN, genetic epidemiology, Genotype, BIOMARKERS, prospective cohort, Nutritional Status, Environmental Sciences & Ecology, lcsh:TX341-641, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, selenoprotein gene variation, Colorectal cancer risk, Article, Colorectal neoplasms, 03 medical and health sciences, Selenium, Seleni, Càncer colorectal, Selenium pathway, medicine, SNP, Humans, Genetic Predisposition to Disease, METAANALYSIS, Aged, Science & Technology, Nutrition & Dietetics, colorectal cancer risk, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710, colorectal neoplasms, Prospective cohort, medicine.disease, POLYMORPHISM, biomarkers, 030104 developmental biology, Frzb, chemistry, Gene Expression Regulation, 3121 General medicine, internal medicine and other clinical medicine, 1111 Nutrition and Dietetics, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Selenoprotein, Environmental Sciences, 0908 Food Sciences, Genètica, Biomarkers, Food Science
Abstract: Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10, PACT significance threshold was P &lt, 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.
Published: 2019

24. Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort

Author: Helena Schock, Kay Tee Kaw, Elisabete Weiderpass, José María Huerta, Eva Ardanaz, Rudolf Kaaks, Carlotta Sacerdote, Petra H.M. Peeters, Dagfinn Aune, Carla H. van Gils, Claudia Agnoli, Heiner Boeing, Anna Karakatsani, Anja Olsen, Antonia Trichopoulou, Mathilde His, Theron Johnson, Renée T. Fortner, Kim Overvad, Antonio Agudo, Anne Tjønneland, Marina Kvaskoff, Elio Riboli, Laure Dossus, Giovanna Masala, Agnès Fournier, Miguel Rodríguez-Barranco, Leire Gil, Carlo La Vecchia, Salvatore Panico, Danja Sarink, Jenny Chang-Claude, Patrick Arveux, Julie A. Schmidt, Rosario Tumino, Fortner, Renée T [0000-0002-1426-8505], Apollo - University of Cambridge Repository, Sarink, Danja, Schock, Helena, Johnson, Theron, Chang-Claude, Jenny, Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Arveux, Patrick, Fournier, Agnè, Kvaskoff, Marina, Boeing, Heiner, Karakatsani, Anna, Trichopoulou, Antonia, La Vecchia, Carlo, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, van Gils, Carla H, Peeters, Petra H M, Weiderpass, Elisabete, Agudo, Antonio, Rodríguez-Barranco, Miguel, Huerta, José María, Ardanaz, Eva, Gil, Leire, Kaw, Kay Tee, Schmidt, Julie A, Dossus, Laure, His, Mathilde, Aune, Dagfinn, Riboli, Elio, Kaaks, Rudolf, and Fortner, Renée T
Subjects: 0301 basic medicine, Oncology, Cancer Research, Epidemiology, PROLACTIN, Cohort Studies, 0302 clinical medicine, Breast cancer, Surgical oncology, Limit of Detection, Reproductive, serum biomarkers of endogenous exposures, biology, Hazard ratio, RANKL, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, BONE METASTASIS, 3. Good health, European Prospective Investigation into Cancer and Nutrition, FACTOR-KAPPA-B, reproductive, hormonal, and related factors, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Cohort, GROWTH, Female, and related factors, Life Sciences & Biomedicine, Serum biomarkers of endogenous exposures, Research Article, EXPRESSION, musculoskeletal diseases, Adult, Risk, medicine.medical_specialty, Breast Neoplasms, lcsh:RC254-282, Càncer de mama, 03 medical and health sciences, Osteoprotegerin, POOR-PROGNOSIS, Internal medicine, Genetics, medicine, Humans, Oncology & Carcinogenesis, Epidemiologia, Aged, Science & Technology, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, RANK Ligand, medicine.disease, hormonal, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, 030104 developmental biology, ESTROGEN-RECEPTOR, Reproductive, hormonal, and related factor, Case-Control Studies, biology.protein, OPG, business, Reproductive, hormonal, and related factors, 1112 Oncology And Carcinogenesis
Abstract: Published version, available at: https://doi.org/10.1186/s12885-018-4887-3 Background Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis. Methods Two thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models. Results Especially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis. Conclusions High pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.
Published: 2018

25. Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence : analysis within EPIC-InterAct across eight European countries

Author: Marc J. Gunter, Daniel B Ibsen, Courtney Dow, Claudia Langenberg, Antonio Agudo, Domenico Palli, José María Huerta, Elena Molina-Portillo, Francesca Mancini, Annemieke M.W. Spijkerman, Robert A. Scott, Miren Dorronsoro, Dagfinn Aune, Fulvio Ricceri, Ju-Sheng Zheng, Ivonne Sluijs, Anna Winkvist, Elio Riboli, Matthias B. Schulze, Nita G. Forouhi, Kay-Tee Khaw, N. Charlotte Onland-Moret, Rosario Tumino, Heiner Boeing, Guy Fagherazzi, Neil Murphy, Anne Tjønneland, Peter M. Nilsson, Sara Grioni, Sherly X. Li, J. Ramón Quirós, Stephen J. Sharp, Salvatore Panico, Eva Ardanaz, Timothy J. Key, Nicholas J. Wareham, Zheng Ye, Fumiaki Imamura, Cecilie Kyrø, Marianne Uhre Jakobsen, Rudolf Kaaks, Alaitz Poveda, Imamura, Fumiaki [0000-0002-6841-8396], Zheng, Jusheng [0000-0001-6560-4890], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Sharp, Stephen [0000-0003-2375-1440], Forouhi, Nita [0000-0002-5041-248X], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Li, Sherly X, Imamura, Fumiaki, Schulze, Matthias B, Zheng, Jusheng, Ye, Zheng, Agudo, Antonio, Ardanaz, Eva, Aune, Dagfinn, Boeing, Heiner, Dorronsoro, Miren, Dow, Courtney, Fagherazzi, Guy, Grioni, Sara, Gunter, Marc J, Huerta, José María, Ibsen, Daniel B, Jakobsen, Marianne Uhre, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Kyrø, Cecilie, Mancini, Francesca Romana, Molina-Portillo, Elena, Murphy, Neil, Nilsson, Peter M, Onland-Moret, N Charlotte, Palli, Domenico, Panico, Salvatore, Poveda, Alaitz, Quirós, J Ramón, Ricceri, Fulvio, Sluijs, Ivonne, Spijkerman, Annemieke M W, Tjonneland, Anne, Tumino, Rosario, Winkvist, Anna, Langenberg, Claudia, Sharp, Stephen J, Riboli, Elio, Scott, Robert A, Forouhi, Nita G, and Wareham, Nicholas J
Subjects: 0301 basic medicine, Dietary Fiber, Male, International Cooperation, Endocrinology, Diabetes and Metabolism, Macronutrient, Physiology, Type 2 diabetes, Diabete, Polyunsaturated fat, 0302 clinical medicine, Endocrinology, Surveys and Questionnaires, insulin resistance, 1114 Paediatrics And Reproductive Medicine, Medicine, Prospective Studies, INDEX, Body mass index, 2. Zero hunger, RISK, diabetes, Diabetes, dietary fibre, Dietary fibre, CASE-COHORT, Single Nucleotide, Middle Aged, Genetic risk score, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diabetes and Metabolism, Europe, INSIGHTS, 1117 Public Health And Health Services, Endokrinologi och diabetes, Female, GRS, Life Sciences & Biomedicine, Type 2, Adult, Interaction, European Continental Ancestry Group, macronutrient, interaction, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, body mass index, Endocrinology and Diabetes, Polymorphism, Single Nucleotide, genetic risk score, Article, White People, 03 medical and health sciences, Endocrinology & Metabolism, BMI, Insulin resistance, Diet, Alleles, Body Mass Index, Diabetes Mellitus, Type 2, Energy Intake, Follow-Up Studies, Humans, Insulin Resistance, Nutrients, Nutrition Assessment, Proportional Hazards Models, Genetic Predisposition to Disease, SDG 3 - Good Health and Well-being, Diabetes mellitus, Genetic predisposition, Diabetes Mellitus, Internal Medicine, Polymorphism, Science & Technology, business.industry, 1103 Clinical Sciences, medicine.disease, 030104 developmental biology, business, diet
Abstract: Aims/hypothesis Gene–macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. Methods We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. Results No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0–51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. Conclusions/interpretation Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.
Published: 2018

26. Measured adiposity in relation to head and neck cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author: Petra H.M. Peeters, Antonio Agudo, Domenico Palli, Ingegerd Johansson, Pagona Lagiou, Peter Wallström, Ulla Westin, Salavatore Panico, Kim Overvad, Sara Grioni, Sylvie Mesrine, Anne Tjønneland, José María Huerta, Clare Pearson, Paolo Vineis, H. Bas Bueno-de-Mesquita, Nerea Larrañaga, Elio Riboli, Heather Ward, Teresa Norat, Guy Fagherazzi, Mattias Johansson, Kathryn E. Bradbury, Christina C. Dahm, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Kuanrong Li, Heiner Boeing, Heinz Freisling, Paul Brennan, Petra A. Wark, Antonia Trichopoulou, Göran Laurell, Nicholas J. Wareham, Rudolf Kaaks, Annika Steffen, Rosario Tumino, Jytte Halkjær, Elisabete Weiderpass, José Ramón Quirós, Eva Ardanaz, María José Sánchez, Marc J. Gunter, David C. Muller, Wareham, Nicholas [0000-0003-1422-2993], Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Ward, Heather A, Wark, Petra A, Muller, David C, Steffen, Annika, Johansson, Mattia, Norat, Teresa, Gunter, Marc J, Overvad, Kim, Dahm, Christina C, Halkjær, Jytte, Tjønneland, Anne, Boutron Ruault, Marie Christine, Fagherazzi, Guy, Mesrine, Sylvie, Brennan, Paul, Freisling, Heinz, Li, Kuanrong, Kaaks, Rudolf, Trichopoulou, Antonia, Lagiou, Pagona, Panico, Salvatore, Grioni, Sara, Tumino, Rosario, Vineis, Paolo, Palli, Domenico, Peeters, Petra H. M, Bueno de Mesquita, H. Ba, Weiderpass, Elisabete, Agudo, Antonio, Quirós, Jose Ramón, Larrañaga, Nerea, Ardanaz, Eva, Huerta, José María, Sánchez, María José, Laurell, Göran, Johansson, Ingegerd, Westin, Ulla, Wallström, Peter, Bradbury, Kathryn E, Wareham, Nicholas J, Khaw, Kay Tee, Pearson, Clare, Boeing, Heiner, Riboli, Elio, University Medical Center Utrecht, and Imperial College Trust
Subjects: Adult, Male, medicine.medical_specialty, obesity, Waist, Epidemiology, Nutritional Status, 030209 endocrinology & metabolism, body mass index, Overweight, Article, White People, head and neck cancers, smoking, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Waist–hip ratio, Risk Factors, Internal medicine, medicine, Journal Article, Humans, Prospective Studies, Prospective cohort study, Adiposity, Aged, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Head and neck cancer, nutritional and metabolic diseases, 11 Medical And Health Sciences, Middle Aged, Anthropometry, medicine.disease, waist circumference, waist:hip ratio, Surgery, European Prospective Investigation into Cancer and Nutrition, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Female, medicine.symptom, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Body mass index
Abstract: BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error. METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: < 22.5 kg/m², normal weight (reference): 22.5-24.9 kg/m², overweight 25-29.9 kg/m², obese: > 30 kg/m²], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models. RESULTS: Among men, a BMI < 22.5 kg/m² was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65). CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated. IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence., 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, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (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), Statistics Netherlands (The Netherlands); ERC- 2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; , PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to K.T. Khaw, N.J. Wareham; C570/A16491 to R.C. Travis and C8221/A19170 to Tim Key (EPIC-Oxford), Medical Research Council (1000143 to K.T. Khaw, N.J. Wareham, MR/M012190/1 to Tim Key (EPIC-Oxford)) (United Kingdom).
Published: 2017

27. Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Author: Klas Sjöberg, Cristina Lasheras, Nicholas J. Wareham, Petra H.M. Peeters, Elisabete Weiderpass, Lutz Schomburg, Sandra Hybsier, Anne Tjønneland, Amanda J. Cross, Christina Bamia, Verena Katzke, Krasimira Aleksandrova, Salvatore Panico, Aurelio Barricarte, Elena Molina-Portillo, José María Huerta, David J. Hughes, Mathilde His, Pagona Lagiou, Kay-Tee Khaw, Antonia Trichopoulou, Dmitry Shungin, Heinz Freisling, Rosario Tumino, Magdalena Stepien, H B As Bueno-de-Mesquita, Catalina Bonet, Ruth C. Travis, Fulvio Ricceri, Tilman Kühn, Mårten Werner, Phlippos Orfanos, Kim Overvad, Bodil Ohlsson, Mazda Jenab, Marie-Christine Boutron-Ruault, Miren Dorronsoro, Domenico Palli, Sabina Sieri, Aurélie Affret, Stepien, Magdalena, Hughes, David J, Hybsier, Sandra, Bamia, Christina, Tjønneland, Anne, Overvad, Kim, Affret, Aurélie, His, Mathilde, Boutron Ruault, Marie Christine, Katzke, Verena, Kühn, Tilman, Aleksandrova, Krasimira, Trichopoulou, Antonia, Lagiou, Pagona, Orfanos, Phlippo, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno de Mesquita, H. B. A, Peeters, Petra H, Weiderpass, Elisabete, Lasheras, Cristina, Bonet Bonet, Catalina, Molina Portillo, Elena, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Ohlsson, Bodil, Sjöberg, Kla, Werner, Mårten, Shungin, Dmitry, Wareham, Nick, Khaw, Kay Tee, Travis, Ruth C, Freisling, Heinz, Cross, Amanda J, Schomburg, Lutz, Jenab, Mazda, Wareham, Nicholas [0000-0003-1422-2993], Khaw, Kay-Tee [0000-0002-8802-2903], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Male, Cancer Research, Epidemiology, Physiology, SERUM COPPER, HEPATITIS-C, 0302 clinical medicine, cancer risk factors, nested case-control study, HEPATOCELLULAR-CARCINOMA, Medicine, Prospective Studies, OXIDATIVE STRESS, BILIARY-TRACT, Aged, Biliary Tract Neoplasms, Carcinoma, Hepatocellular, Case-Control Studies, Copper, Europe, Female, Humans, Liver Neoplasms, Middle Aged, Zinc, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, biology, zinc, Public Health, Global Health, Social Medicine and Epidemiology, hepatocellular carcinoma, Micronutrient, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Life Sciences & Biomedicine, prospective cohort, Serum copper, chemistry.chemical_element, CERULOPLASMIN, 03 medical and health sciences, RATIO, INFLAMMATION, Journal Article, COHORT, Oncology & Carcinogenesis, FATTY LIVER-DISEASE, Cancer och onkologi, Science & Technology, business.industry, Carcinoma, Case-control study, Hepatocellular, nested case–control study, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 030104 developmental biology, chemistry, Cancer and Oncology, copper, Immunology, biology.protein, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Ceruloplasmin, 1112 Oncology And Carcinogenesis
Abstract: This work was supported by the French National Cancer Institute (L'Institut National du Cancer; INCA; grant number 2009-139; PI: M Jenab) and the Health Research Board of Ireland (award number HRA_PHS/2013/397; PI: DJ Hughes). 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, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (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), Statistics Netherlands (The Netherlands); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk and MR/M012190/1 to EPIC- Oxford) (UK); Medical Research Council (1000143 to EPIC- Norfolk) (UK). For information on how to submit an application for gaining access to EPIC data and/or bio-specimens, please follow the instructions at http://epic.iarc.fr/access/index.php, Stepien, M., Hughes, D.J., Hybsier, S., Bamia, C., Tjønneland, A., Overvad, K., Affret, A., His, M., Boutron-Ruault, M.-C., Katzke, V., Kühn, T., Aleksandrova, K., Trichopoulou, A., Lagiou, P., Orfanos, P., Palli, D., Sieri, S., Tumino, R., Ricceri, F., Panico, S., Bueno-De-Mesquita, H.B., Peeters, P.H., Weiderpass, E., Lasheras, C., Bonet Bonet, C., Molina-Portillo, E., Dorronsoro, M., Huerta, J.M., Barricarte, A., Ohlsson, B., Sjöberg, K., Werner, M., Shungin, D., Wareham, N., Khaw, K.-T., Travis, R.C., Freisling, H., Cross, A.J., Schomburg, L., Jenab, M.
Published: 2017

28. Diet quality scores and prediction of all-cause, cardiovascular and cancer mortality in a pan-european cohort study

Author: Lassale, Camille, Gunter, Marc J., Romaguera, Dora, Peelen, Linda M., Van der Schouw, Yvonne T., Beulens, Joline W. J., Freisling, Heinz, Muller, David C., Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Affret, Aurelie, Overvad, Kim, Dahm, Christina C., Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K., Katzke, Verena A., Kuehn, Tilman, Buijsse, Brian, Quiros, Jose-Ramon, Sanchez-Cantalejo, Emilio, Etxezarreta, Nerea, Maria Huerta, Jose, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay-Tee, Key, Timothy J., Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Boer, Jolanda M. A., Sonestedt, Emily, Nilsson, Lena Maria, Renstrom, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M., Riboli, Elio, Tzoulaki, Ioanna, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Lassale, Camille, Gunter, Marc J, Romaguera, Dora, Peelen, Linda M, Van der Schouw, Yvonne T, Beulens, Joline W. J, Freisling, Heinz, Muller, David C, Ferrari, Pietro, Huybrechts, Inge, Fagherazzi, Guy, Boutron Ruault, Marie Christine, Affret, Aurélie, Overvad, Kim, Dahm, Christina C, Olsen, Anja, Roswall, Nina, Tsilidis, Konstantinos K, Katzke, Verena A, Kühn, Tilman, Buijsse, Brian, Quirós, José Ramón, Sánchez Cantalejo, Emilio, Etxezarreta, Nerea, Huerta, José María, Barricarte, Aurelio, Bonet, Catalina, Khaw, Kay Tee, Key, Timothy J, Trichopoulou, Antonia, Bamia, Christina, Lagiou, Pagona, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno de Mesquita, H. Ba, Boer, Jolanda M. A, Sonestedt, Emily, Nilsson, Lena Maria, Renström, Frida, Weiderpass, Elisabete, Skeie, Guri, Lund, Eiliv, Moons, Karel G. M, Riboli, Elio, Tzoulaki, Ioanna, [Lassale,C, Gunter,MJ, Romaguera,D, Tsilidis,KK, Riboli,E, Tzoulaki,I] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Palma de Mallorca, Spain. [Romaguera,D, Quirós,J, Sánchez-Cantalejo,E, Etxezarreta,N, Huerta,JM, Barricarte,A, Bonet,C] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Peelen,LM, Schouw,ITV, Beulens,JWJ, Moons,KGM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.[Freisling,H, Muller,DC, Ferrari,P, Huybrechts,I] International Agency for Research on Cancer, Lyon, France. [Fagherazz,G, Boutron-Ruault,M, Affret,A] Institut National de la Santé et de la Recherche Médicale, Center for Research in Epidemiology and Population, Health, Villejuif, France. Institut Gustave Roussy, Villejuif, France. Paris South University, Unité Mixte de Recherche, Villejuif, France. [Overvad,K, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Olsen,A, Roswall,N] Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark. [Tsilidis,KK] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany. [Katzke,VA, Kühn,T] Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke German Institute of Human Nutrition, Potsdam, Germany. [Buijsse,B] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Quirós,R] Public Health Directorate, Asturias, Oviedo, Spain. [Sánchez-Cantalejo,E] Andalusian School of Public Health, Granada, Spain. [Etxezarreta,N] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Bonet,C] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Cambridge, United Kingdom. [Key,J] Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. [Trichopoulou,A, Bamia,C, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. Hellenic Health Foundation, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Department of Preventive and Predictive Medicine, Foundation of the Carlo Besta Neurological Institute, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic MP Arezzo' Hospital, Ragusa, Italy. [Fasanelli,F] Human Genetics Foundation, Turin, Italy. [Bueno-de-Mesquita,HB, Boer,JMA] Center for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment, Bilthoven, Netherlands. [Sonestedt,E] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [Nilsson,LM, Renström,F] Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, 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. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO) 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), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (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), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), 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: Male, humanos, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Social Sciences, Índice de masa corporal, Global Health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, distribución por sexos, Mathematical and Statistical Techniques, Sociology, Risk Factors, Neoplasms, Medicine and Health Sciences, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity [Medical Subject Headings], Public and Occupational Health, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], Estado Nutricional, estudios de cohortes, mediana edad, Factores de Riesgo, neoplasias, Medicine(all), Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Agricultural and Biological Sciences(all), dieta, Agriculture, Public Health, Global Health, Social Medicine and Epidemiology, Estudios Prospectivos, Plants, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Neoplasias, Näringslära, Cardiovascular Diseases, Hábitos alimenticios, estilo de vida, Physical Sciences, Medicine, Dieta, Female, Statistics (Mathematics), Research Article, 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], General Science & Technology, Science, Estudios de cohortes, European Continental Ancestry Group, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], enfermedades cardiovasculares, Crops, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research and Analysis Methods, White People, Education, Fruits, Age Distribution, distribución por edades, SDG 3 - Good Health and Well-being, MD Multidisciplinary, Anatomy::Cardiovascular System [Medical Subject Headings], Journal Article, factores de riesgo, Humans, Statistical Methods, Sex Distribution, Life Style, Educational Attainment, Nutrition, Sistema cardiovascular, Biochemistry, Genetics and Molecular Biology(all), Organisms, Biology and Life Sciences, Physical Activity, Nutrients, Actividad motora, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Feeding Behavior::Food Habits [Medical Subject Headings], Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Hábito de Fumar, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, grupo de ascendencia continental europea, Mathematics, Forecasting, Crop Science
Abstract: Scores of overall diet quality have received increasing attention in relation to disease aetiology; however, their value in risk prediction has been little examined. The objective was to assess and compare the association and predictive performance of 10 diet quality scores on 10-year risk of all-cause, CVD and cancer mortality in 451,256 healthy participants to the European Prospective Investigation into Cancer and Nutrition, followed-up for a median of 12.8y. All dietary scores studied showed significant inverse associations with all outcomes. The range of HRs (95% CI) in the top vs. lowest quartile of dietary scores in a composite model including non-invasive factors (age, sex, smoking, body mass index, education, physical activity and study centre) was 0.75 (0.72-0.79) to 0.88 (0.84-0.92) for all-cause, 0.76 (0.69-0.83) to 0.84 (0.76-0.92) for CVD and 0.78 (0.73-0.83) to 0.91 (0.85-0.97) for cancer mortality. Models with dietary scores alone showed low discrimination, but composite models also including age, sex and other non-invasive factors showed good discrimination and calibration, which varied little between different diet scores examined. Mean C-statistic of full models was 0.73, 0.80 and 0.71 for all-cause, CVD and cancer mortality. Dietary scores have poor predictive performance for 10-year mortality risk when used in isolation but display good predictive ability in combination with other non-invasive common risk factors., The coordination of EPIC is financially supported by the European Commission (D-GSANCO) 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); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC- Italy and National Research Council (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), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); 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).
Published: 2016

29. Prospective association of liver function biomarkers with development of hepatobiliary cancers

Author: Petra H.M. Peeters, José María Huerta, Amanda J. Cross, Bodil Ohlsson, Elisabeth Trepo, H. Bas Bueno-de-Mesquita, Vassiliki Benetou, Anja Olsen, Krasimira Aleksandrova, Heiner Boeing, Veronika Fedirko, Magdalena Stepien, Mazda Jenab, Pietro Ferrari, Hanna Nyström, Klas Sjöberg, Guy Fagherazzi, Isabelle Romieu, Elio Riboli, Kim Overvad, Rudolf Kaaks, Timothy J. Key, Heinz Freisling, Antoine Racine, Salvatore Panico, Rosario Tumino, Miren Dorronsoro, Kay-Tee Khaw, Tilman Kühn, Antonia Trichopoulou, Marc J. Gunter, Elisabete Weiderpass, Mårten Werner, Marie-Christine Boutron-Ruault, Talita Duarte-Salles, María José Sánchez, Pagona Lagiou, J. Ramón Quirós, Dimitrios Trichopoulos, Christina Bamia, Eva Ardanaz, Anne Tjønneland, Osmel Companioni Nápoles, Domenico Palli, Sara Grioni, Alessio Naccarati, Eiliv Lund, University Medical Center Utrecht, Imperial College Trust, Stepien, Magdalena, Fedirko, Veronika, Duarte Salles, Talita, Ferrari, Pietro, Freisling, Heinz, Trepo, Elisabeth, Trichopoulou, Antonia, Bamia, Christina, Weiderpass, Elisabete, Olsen, Anja, Tjønneland, Anne, Overvad, Kim, Boutron Ruault, Marie Christine, Fagherazzi, Guy, Racine, Antoine, Kühn, Tilman, Kaaks, Rudolf, Aleksandrova, Krasimira, Boeing, Heiner, Lagiou, Pagona, Benetou, Vassiliki, Trichopoulos, Dimitrio, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Bueno de Mesquita, H. Ba, Peeters, Petra H, Lund, Eiliv, Quirós, J. Ramón, Nápoles, Osmel Companioni, Sánchez, María José, Dorronsoro, Miren, Huerta, José María, Ardanaz, Eva, Ohlsson, Bodil, Sjöberg, Kla, Werner, Mårten, Nystrom, Hanna, Khaw, Kay Tee, Key, Timothy J, Gunter, Marc, Cross, Amanda, Riboli, Elio, Romieu, Isabelle, and Jenab, Mazda
Subjects: 0301 basic medicine, Male, Cancer Research, Epidemiology, ALANINE AMINOTRANSFERASE, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, Risk Factors, HEPATOCELLULAR-CARCINOMA, EPIDEMIOLOGY, Prospective Studies, Gamma-glutamyltransferase, Non-U.S. Gov't, BILIARY-TRACT, POPULATION, Public, Environmental & Occupational Health, Aged, 80 and over, education.field_of_study, Biological markers, medicine.diagnostic_test, biology, Research Support, Non-U.S. Gov't, Liver Neoplasms, food and beverages, Alanine Transaminase, gamma-Glutamyltransferase, Hepatobiliary cancer, Middle Aged, Multicenter Study, Europe, Biliary Tract Neoplasms, Oncology, BILIRUBIN, 1117 Public Health And Health Services, Biliary Tract Neoplasm, Liver Neoplasm, Biliary tract, 030220 oncology & carcinogenesis, Liver function test, Alkaline phosphatase, Nested case-control study, Female, Case-Control Studie, Life Sciences & Biomedicine, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Bilirubin, Population, GAMMA-GLUTAMYL-TRANSFERASE, Research Support, digestive system, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Journal Article, Humans, Comparative Study, COHORT, Aspartate Aminotransferases, education, Bile Duct Neoplasm, Aged, Science & Technology, business.industry, Risk Factor, Aspartate Aminotransferase, DIABETES-MELLITUS, Biomarker, Prospective cohort, Alkaline Phosphatase, digestive system diseases, Biological marker, Prospective Studie, 030104 developmental biology, Endocrinology, chemistry, Alanine transaminase, Bile Duct Neoplasms, Case-Control Studies, biology.protein, RISK-FACTORS, Liver function, Liver function tests, business, 1112 Oncology And Carcinogenesis, Biomarkers
Abstract: INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.
Published: 2016

30. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Murphy, N, Cross, A, Abubakar, M, Jenab, M, Aleksandrova, K, Boutron-Ruault, M, Dossus, L, Racine, A, Kühn, T, Katzke, V, Tjønneland, A, Petersen, K, Overvad, K, Quirós, JR, Jakszyn, P, Molina-Montes, E, Dorronsoro, M, Huerta, J, Barricarte, A, Khaw, K, Wareham, N, Travis, R, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Masala, G, Krogh, V, Tumino, R, Vineis, P, Panico, S, Bueno-de-Mesquita, H, Siersema, P, Peeters, P, Ohlsson, B, Ericson, U, Palmqvist, R, Nyström, H, Weiderpass, E, Skeie, G, Freisling, H, Kong, S, Tsilidis, K, Muller, D, Riboli, E, Gunter, M, [Murphy,N, Cross,AJ, Vineis,P, Bueno-de-Mesquita,HB, Tsilidis,K, Riboli,E, Gunter,MJ] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.[Abubakar,M] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom. [Jenab,M, Freisling,M, Kong,SY, Mulle,DC, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany. [Boutron-Ruault,M, Dossus,L, Racine,A] Inserm, Nutrition, Hormones and Women’s Health, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France. Université Paris Sud, UMRS 1018, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Kühn,T, Katzke,VA] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Petersen,KEN] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Montes,E] Andalusian School of Public Health, Granada, Spain. [Molina-Montes,E, Huerta,J, Barricarte,A] Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia–CIBERESP, Basque Regional Health Department, Vitoria, Spain. [Huerta,J] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] University of Cambridge, Cambridge, United Kingdom. [Wareham,N] MRC Epidemiology Unit, Cambridge, United Kingdom. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Masala,G] 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, Civic–M.P.Arezzo Hospital, Azienda Sanitaria Provinciale di Ragusa, Italy. [Vineis,P] HuGeF Foundation, Torino, Italy. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy. [Bueno-de- Mesquita,HB] Department of Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease–Genetic Epidemiology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Lund University, Sweden. [Palmqvist,R, Nyström,H] Medical Bioscience, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø–The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland. [Tsilidis,K] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO), and the International Agency for Research on Cancer., University Medical Center Utrecht, Imperial College Trust, Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron Ruault, Marie Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina E. N, Overvad, Kim, Quirós, J. Ramón, Jakszyn, Paula, Molina Montes, Esther, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kosta, Muller, David C, Riboli, Elio, Gunter, Marc J., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Male, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Cell- och molekylärbiologi, Obesidad, Biochemistry, Body Mass Index, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Endocrinology, Odds Ratio, Insulin, Prospective Studies, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Adiposity, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, C-Peptide, Incidence, 11 Medical And Health Sciences, Oncology, Medicine, Waist Circumference, Fenotipo, Human, Logistic Model, Colon, Risk Assessment, Hyperinsulinism, Gastrointestinal Tumors, Neoplasias Colorrectales, Humans, Comparative Study, Diseases::Cardiovascular Diseases [Medical Subject Headings], Protective Factor, Cancer och onkologi, Chi-Square Distribution, Biology and Life Sciences, nutritional and metabolic diseases, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Biomarker, Hormones, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Logistic Models, Case-Control Studies, Cancer and Oncology, Digestive System, Biomarkers, Cell and Molecular Biology, Metabolic Processes, Physiology, Health Status, Colorectal Neoplasm, Health Statu, Risk Factors, Medicine and Health Sciences, Body Size, Multivariate Analysi, Tamaño Corporal, Enfermedades Cardiovasculares, Medicine(all), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Research Support, Non-U.S. Gov't, Estudios de Casos y Controles, Estudios Prospectivos, Middle Aged, Multicenter Study, Europe, Phenotype, Physiological Parameters, Female, Anatomy, Colorectal Neoplasms, Case-Control Studie, Research Article, 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], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size [Medical Subject Headings], Rectal Cancer, Research Support, N.I.H., Extramural, General & Internal Medicine, Journal Article, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism [Medical Subject Headings], Obesity, Colorectal Cancer, Diabetic Endocrinology, Obesity, Metabolically Benign, Hiperinsulinismo, Risk Factor, Body Weight, Cancers and Neoplasms, Protective Factors, Gastrointestinal Tract, Metabolism, Sobrepeso, Multivariate Analysis, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Prevalencia
Abstract: Background Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. Methods and Findings The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of, Gunter and colleagues analyse a large European dataset to determine how body size and metabolic profile associates with the risk of developing colorectal cancer., Editors' Summary Background Colorectal cancer is the third most common cancer worldwide and is a leading cause of cancer-related death, killing around 700,000 people every year. It develops when cells in the colon (the final part of the digestive system, which is also known as the large intestine or large bowel) or the rectum (the lower end of the colon) acquire genetic changes that allow them to divide uncontrollably to form a tumor and to move around the body (metastasize). Symptoms of colorectal cancer include blood in the stool, a change in bowel habits, and unexplained weight loss. Treatments for colorectal cancer include surgery, chemotherapy, and radiation. As with other types of cancer, these treatments are more likely to be successful if started when the tumor is very small. Consequently, many countries run screening programs that use colonoscopy, the fecal occult blood test, and other tests to detect the earliest signs of colorectal cancer in apparently healthy people. Why Was This Study Done? Being obese—having too much body fat—is associated with an increased colorectal cancer risk (other risk factors include age, having a family history of colorectal cancer, and eating a high-fat, low-fiber diet). Obesity is also associated with several other chronic diseases, and recent evidence suggests that some obese individuals have a higher risk of developing these diseases than others. For example, overweight/obese individuals who have hyperinsulinemia (abnormally high blood levels of insulin; “metabolically unhealthy”) seem to have a higher risk of cardiovascular disease than their non-hyperinsulinemic (“metabolically healthy”) overweight counterparts. If certain combinations of metabolic health status and body size (“metabolically defined body size phenotypes”) are also associated with colorectal cancer, measurement of insulin levels in conjunction with body fat (adiposity) measurements such as body mass index (BMI; an indicator of body fat calculated by dividing a person’s weight in kilograms by their height in meters squared) might improve colorectal cancer risk assessment. In this nested case–control study, the researchers assess the associations between metabolically defined body size phenotypes and colorectal cancer risk. A nested case–control study identifies everyone in a group (here, participants in the European Prospective Investigation into Cancer and Nutrition [EPIC] study) who has a specific condition, identifies matched individuals in the same group without the condition, and asks whether these controls and the cases differ in terms of a specific characteristic or outcome. What Did the Researchers Do and Find? The researchers matched 737 participants in the EPIC study who developed colorectal cancer after study enrollment with 737 controls and used serum concentrations of C-peptide, a marker of insulin secretion, and BMI measurements to classify each individual as metabolically healthy/normal weight, metabolically healthy/overweight, metabolically unhealthy/normal weight, or metabolically unhealthy/overweight. Specifically, the researchers categorized people as metabolically unhealthy if they had a C-peptide level above an arbitrarily chosen cut-off value based on the distribution of C-peptide levels in the control participants and as overweight if they had a BMI of ≥25 kg/m2 (the standard definition of overweight). Compared to metabolically healthy normal weight individuals, metabolically unhealthy normal weight and overweight individuals had an increased colorectal cancer risk; metabolically healthy overweight individuals had a similar colorectal cancer risk to metabolically healthy normal weight individuals. Among overweight individuals, metabolically healthy individuals had a lower colorectal cancer risk than metabolically unhealthy individuals. Finally, similar associations were seen when the researchers used waist circumference instead of BMI as the measure of adiposity. What Do These Findings Mean? These findings suggest that normal weight individuals with hyperinsulinemia (the metabolically unhealthy normal weight phenotype) have a higher risk of colorectal cancer than normal weight individuals without hyperinsulinemia. They also suggest that metabolically unhealthy overweight individuals have a higher risk of colorectal cancer than metabolically healthy overweight individuals. The accuracy of these findings may be limited by the method the researchers used to classify individuals as hyperinsulinemic—there is no universally accepted clinical definition for using C-peptide level to diagnose hyperinsulinemia. Nevertheless, these findings suggest that the assessment of insulin levels in conjunction with adiposity measures might be a better way to assess an individual’s colorectal cancer risk than simply measuring adiposity, and might help to identify those individuals at high risk of colorectal cancer who are most likely to benefit from targeted interventions designed to prevent the onset of clinical disease. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001988. The US National Cancer Institute provides information for patients about all aspects of colorectal cancer; it also provides more detailed information colorectal cancer for health professionals and information on cancer risk and obesity The UK National Health Service Choices website has information and personal stories about colorectal cancer and information on obesity The not-for-profit organization Cancer Research UK provides information about colorectal cancer and about the association between cancer and obesity MedlinePlus provides links to further resources about colorectal cancer and about obesity Wikipedia has a page on hyperinsulinemia (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) More information about the EPIC study is available
Published: 2016

31. Interaction of dietary and genetic factors influencing body iron status and risk of type 2 diabetes within the EPIC-InterAct study

Author: Kim Overvad, Courtney Dow, Amanda J. Cross, José María Huerta, Heiner Boeing, Elio Riboli, Karina Meidtner, Janine Kröger, Magdalena Stepien, Paula Jakszyn, Verena Katzke, Timothy J. Key, Guy Fagherazzi, Olle Melander, Francesca Mancini, Benedetta Bendinelli, Cecilie Kyrø, Domenico Palli, Marc J. Gunter, Paul W. Franks, Stephen J. Sharp, Salvatore Panico, Anne Tjønneland, Kay-Tee Khaw, Claudia Langenberg, Peter M. Nilsson, Mazda Jenab, Aurelio Barricarte, Rosario Tumino, Kim Ekblom, Matthias B. Schulze, J. Ramón Quirós, Yvonne T. van der Schouw, Tilman Kühn, Claudia Agnoli, Miguel Rodríguez-Barranco, Ivonne Sluijs, Carlotta Sacerdote, Clara Podmore, Nicholas J. Wareham, Larraitz Arriola, Nita G. Forouhi, Podmore, Clara [0000-0002-2452-8067], Khaw, Kay-Tee [0000-0002-8802-2903], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Imperial College Trust, Commission of the European Communities, Meidtner, Karina, Podmore, Clara, Kröger, Janine, Van Der Schouw, Yvonne T., Bendinelli, Benedetta, Agnoli, Claudia, Arriola, Larraitz, Barricarte, Aurelio, Boeing, Heiner, Cross, Amanda J., Dow, Courtney, Ekblom, Kim, Fagherazzi, Guy, Franks, Paul W., Gunter, Marc J., Huerta, José María, Jakszyn, Paula, Jenab, Mazda, Katzke, Verena A., Key, Timothy J., Khaw, Kay Tee, Kühn, Tilman, Kyrø, Cecilie, Mancini, Francesca Romana, Melander, Olle, Nilsson, Peter M., Overvad, Kim, Palli, Domenico, Panico, Salvatore, Ramón Quirós, J., Rodríguez-Barranco, Miguel, Sacerdote, Carlotta, Sluijs, Ivonne, Stepien, Magdalena, Tjonneland, Anne, Tumino, Rosario, Forouhi, Nita G., Sharp, Stephen J., Langenberg, Claudia, Schulze, Matthias B., Riboli, Elio, and Wareham, Nicholas J.
Subjects: 0301 basic medicine, Male, Hemochromatosis Protein/genetics, Candidate gene, Endocrinology, Diabetes and Metabolism, STORES, Genome-wide association study, Type 2 diabetes, MEAT CONSUMPTION, Cohort Studies, Risk Factors, Medicine, 11 Medical and Health Sciences, chemistry.chemical_classification, biology, Transferrin, ASSOCIATION, Middle Aged, CANCER, HEME, Europe, Female, FERRITIN, Life Sciences & Biomedicine, PROJECT, medicine.medical_specialty, Iron, Single-nucleotide polymorphism, METABOLISM, Polymorphism, Single Nucleotide, Article, Europe/epidemiology, Transferrin/genetics, 03 medical and health sciences, Endocrinology & Metabolism, Internal medicine, Journal Article, Internal Medicine, Humans, Hemochromatosis Protein, POLYMORPHISMS, Genetic association, Advanced and Specialized Nursing, Science & Technology, business.industry, Transferrin saturation, medicine.disease, Diet, Ferritin, Ferritins/genetics, 030104 developmental biology, Endocrinology, Cross-Sectional Studies, Diabetes Mellitus, Type 2/epidemiology, chemistry, Diabetes Mellitus, Type 2, Ferritins, biology.protein, Gene-Environment Interaction, business, Iron/metabolism, Genome-Wide Association Study
Abstract: OBJECTIVE Meat intake has been consistently shown to be positively associated with incident type 2 diabetes. Part of that association may be mediated by body iron status, which is influenced by genetic factors. We aimed to test for interactions of genetic and dietary factors influencing body iron status in relation to the risk of incident type 2 diabetes. RESEARCH DESIGN AND METHODS The case-cohort comprised 9,347 case subjects and 12,301 subcohort participants from eight European countries. Single nucleotide polymorphisms (SNPs) were selected from genome-wide association studies on iron status biomarkers and candidate gene studies. A ferritin-related gene score was constructed. Multiplicative and additive interactions of heme iron and SNPs as well as the gene score were evaluated using Cox proportional hazards regression. RESULTS Higher heme iron intake (per 1 SD) was associated with higher ferritin levels (β = 0.113 [95% CI 0.082; 0.144]), but not with transferrin (−0.019 [−0.043; 0.006]) or transferrin saturation (0.016 [−0.006; 0.037]). Five SNPs located in four genes (rs1799945 [HFE H63D], rs1800562 [HFE C282Y], rs236918 [PCK7], rs744653 [SLC40A1], and rs855791 [TMPRSS6 V736A]) were associated with ferritin. We did not detect an interaction of heme iron and the gene score on the risk of diabetes in the overall study population (Padd = 0.16, Pmult = 0.21) but did detect a trend toward a negative interaction in men (Padd = 0.04, Pmult = 0.03). CONCLUSIONS We found no convincing evidence that the interplay of dietary and genetic factors related to body iron status associates with type 2 diabetes risk above the level expected from the sum or product of the two individual exposures.
Published: 2018

32. 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

33. A Mendelian randomization study of circulating uric acid and type 2 diabetes

Author: Lotte Maxild Mortensen, Aurelio Barricarte, Elio Riboli, J. Ramón Quirós, Peter M. Nilsson, Françoise Clavel-Chapelon, Yvonne T. van der Schouw, Diana Gavrila, Larraitz Arriola, Nita G. Forouhi, Michael V. Holmes, Esther Molina-Montes, Joline W.J. Beulens, Kim Overvad, Beverley Balkau, José María Huerta, Carlotta Sacerdote, Rudolf Kaaks, Olov Rolandsson, Sabina Sieri, Daphne L. van der A, Stephen J. Sharp, Kay T ee Khaw, Salvatore Panico, Ivonne Sluijs, Claudia Langenberg, Domenico Palli, Nicholas J. Wareham, Guy Fagherazzi, Julie A. Schmidt, Rosario Tumino, Folkert W. Asselbergs, Annemieke M.W. Spijkerman, Robert A. Scott, Anne Tjønneland, Ruth C. Travis, Núria Sala, Tilman Kühn, Heiner Boeing, Tom Palmer, Nadia Slimani, Paul W. Franks, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Sluijs, Ivonne, Holmes, Michael V, van der Schouw, Yvonne T, Beulens, Joline W. J, Asselbergs, Folkert W, Huerta, José María, Palmer, Tom M, Arriola, Larraitz, Balkau, Beverley, Barricarte, Aurelio, Boeing, Heiner, Clavel Chapelon, Françoise, Fagherazzi, Guy, Franks, Paul W, Gavrila, Diana, Kaaks, Rudolf, Khaw, Kay Tee, Kühn, Tilman, Molina Montes, Esther, Mortensen, Lotte Maxild, Nilsson, Peter M, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Quirós, J. Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Sala, Núria, Schmidt, Julie A, Scott, Robert A, Sieri, Sabina, Slimani, Nadia, Spijkerman, Annemieke M. W, Tjonneland, Anne, Travis, Ruth C, Tumino, Rosario, van der A, Daphne L, Sharp, Stephen J, Forouhi, Nita G, Langenberg, Claudia, Riboli, Elio, and Wareham, Nicholas J.
Subjects: Male, Endocrinology, Diabetes and Metabolism, BLOOD-PRESSURE, Type 2 diabetes, DISEASE, chemistry.chemical_compound, Medicine, Prospective Studies, Non-U.S. Gov't, METABOLIC SYNDROME, Medicine(all), CARDIOVASCULAR RISK, Research Support, Non-U.S. Gov't, Confounding, Mendelian Randomization Analysis, 11 Medical And Health Sciences, Middle Aged, EXCESSIVE FRUCTOSE INTAKE, Female, Life Sciences & Biomedicine, Human, Adult, medicine.medical_specialty, Diabetes risk, ASSOCIATION ANALYSES IDENTIFY, SERUM URATE, TRANSPORTER SLC2A9, Research Support, Endocrinology & Metabolism, Diabetes mellitus, Internal medicine, Mendelian randomization, Internal Medicine, Journal Article, Humans, Genetic Predisposition to Disease, Mendelian Randomization Analysi, Science & Technology, business.industry, INSTRUMENTS, InterAct Consortium, medicine.disease, Uric Acid, Prospective Studie, Endocrinology, chemistry, Diabetes Mellitus, Type 2, Genetic Loci, Uric acid, Metabolic syndrome, NO EVIDENCE, business
Abstract: We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid–associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 [95% CI 0.87, 1.16]). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid–lowering therapies may therefore not be beneficial in reducing diabetes risk.
Published: 2015

34. Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: results from the EPIC cohort study

Author: Sanikini, H., Dik, V.K., Siersema, P.D., Bhoo-Pathy, N., Uiterwaal, C.S., Peeters, P.H.M., Gonzalez, C.A., Zamora-Ros, R., Overvad, K., Tjonneland, A., Roswall, N., Boutron-Ruault, M.C., Fagherazzi, G., Racine, A., Kuhn, T., Katzke, V., Boeing, H., Trichopoulou, A., Trichopoulos, D., Lagiou, P., Palli, D., Grioni, S., Vineis, P., Tumino, R., Panico, S., Weiderpass, E., Skeie, G., Braaten, T., Huerta, J.M., Sanchez-Cantalejo, E., Barricarte, A., Sonestedt, E., Wallstrom, P., Nilsson, L.M., Johansson, I., Bradbury, K.E., Khaw, K.T., Wareham, N., Huybrechts, I., Freisling, H., Cross, A.J., Riboli, E., Bueno-de-Mesquita, H.B., Sanikini, Harinakshi, Dik, Vincent K, Siersema, Peter D, Bhoo Pathy, Nirmala, Uiterwaal, Cuno S. P. M, Peeters, Petra H. M, González, Carlos A, Zamora Ros, Raul, Overvad, Kim, Tjønneland, Anne, Roswall, Nina, Boutron Ruault, Marie Christine, Fagherazzi, Guy, Racine, Antoine, Kühn, Tilman, Katzke, Verena, Boeing, Heiner, Trichopoulou, Antonia, Trichopoulos, Dimitrio, Lagiou, Pagona, Palli, Domenico, Grioni, Sara, Vineis, Paolo, Tumino, Rosario, Panico, Salvatore, Weiderpass, Elisabete, Skeie, Guri, Braaten, Tonje, Huerta, José María, Sánchez Cantalejo, Emilio, Barricarte, Aurelio, Sonestedt, Emily, Wallstrom, Peter, Nilsson, Lena Maria, Johansson, Ingegerd, Bradbury, Kathryn E, Khaw, Kay Tee, Wareham, Nick, Huybrechts, Inge, Freisling, Heinz, Cross, Amanda J, Riboli, Elio, and Bueno de Mesquita, H. B.
Subjects: Adult, Male, Risk, tea, coffee, UNITED-STATES, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], ALCOHOL, Cohort Studies, HELICOBACTER-PYLORI, Stomach Neoplasms, Stomach Neoplasm, Caffeine, Humans, Prospective Studies, METAANALYSIS, Proportional Hazards Models, decaffeinated coffee, gastric cancer, CONSUMPTION, ADENOCARCINOMA, European Prospective Investigation into Cancer and Nutrition, Middle Aged, BLACK TEA, caffeinated coffee, Prospective Studie, STOMACH-CANCER, Proportional Hazards Model, ESOPHAGUS, Female, SMOKING, Cohort Studie, Human
Abstract: Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%-confidence intervals [CI]: 0.84-1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%-CI: 0.82-1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%-CI: 0.75-1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%-CI: 0.59-1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%-CI: 1.03-1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%-CI: 1.16-3.36, p-trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%-CI: 1.04-1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding. What's New? Can drinking coffee or tea lead to cancer? Can they protect against cancer? These popular drinks certainly contain antioxidants, but despite many investigations into the question, we still have no clear answer. A new study has plied the data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in search of a link. Participants self-reported their coffee and tea consumption by questionnaire. The authors found no link between drinking tea or coffee - with or without caffeine - and overall risk of gastric cancer; they did discern a slight increase in gastric cardia cancer with consumption of caffeinated coffee.
Published: 2015

35. Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Guri Skeie, Petra H.M. Peeters, Khalid Iqbal, José María Huerta, Aurélie Affret, Ruth C. Travis, Amanda J. Cross, Rosario Tumino, Kim Overvad, María José Sánchez, Inge Huybrechts, José Ramón Quirós, Weimin Ye, Marie-Christine Boutron-Ruault, Genevieve Buckland, Elio Riboli, Salvatore Panico, Esther Molina-Montes, Pilar Amiano, Eric J. Duell, Kay-Tee Khaw, Nicholas J. Wareham, Mathilde His, Heather Ward, Heinz Freisling, Tilman Kühn, Antonia Trichopoulou, Hendrik B. Bueno-de-Mesquita, Domenico Palli, Elisabete Weiderpass, Effie Vasilopoulou, Anne Tjønneland, Kristina E.N. Petersen, Verena Katzke, Emily Sonestedt, Claudia Agnoli, Christina Bamia, Bodil Ohlsson, Heiner Boeing, Petra A. Wark, Malin Sund, Eva Ardanaz, Carlotta Sacerdote, University Medical Center Utrecht, Imperial College Trust, Molina Montes, Esther, Sánchez, María José, Buckland, Genevieve, Bueno de Mesquita, H. B. A, Weiderpass, Elisabete, Amiano, Pilar, Wark, Petra A, Kühn, Tilman, Katzke, Verena, Huerta, José María, Ardanaz, Eva, Quirós, José Ramón, Affret, Aurélie, His, Mathilde, Boutron Ruault, Marie Christine, Peeters, Petra H, Ye, Weimin, Sund, Malin, Boeing, Heiner, Iqbal, Khalid, Ohlsson, Bodil, Sonestedt, Emily, Tjønneland, Anne, Petersen, Kristina En, Travis, Ruth C, Skeie, Guri, Agnoli, Claudia, Panico, Salvatore, Palli, Domenico, Tumino, Rosario, Sacerdote, Carlotta, Freisling, Heinz, Huybrechts, Inge, Overvad, Kim, Trichopoulou, Antonia, Bamia, Christina, Vasilopoulou, Effie, Wareham, Nick, Khaw, Kay Tee, Cross, Amanda J, Ward, Heather A, Riboli, Elio, Duell, Eric J., Wareham, Nicholas [0000-0003-1422-2993], Khaw, Kay-Tee [0000-0002-8802-2903], and Apollo - University of Cambridge Repository
Subjects: Male, Oncology, Cancer Research, Mediterranean diet, Epidemiology, pancreatic cancer, Diet, Mediterranean, EPIC COHORT, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, PARTICIPANTS, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Pancreas cancer, POPULATION, 2. Zero hunger, education.field_of_study, Middle Aged, Prognosis, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Female, Life Sciences & Biomedicine, Cohort study, COUNTRIES, medicine.medical_specialty, Population, White People, 03 medical and health sciences, Mediterranean cooking, Breast cancer, ADHERENCE, SDG 3 - Good Health and Well-being, Internal medicine, Pancreatic cancer, Cuina mediterrània, medicine, cohort study, Journal Article, Humans, BREAST-CANCER, Oncology & Carcinogenesis, education, Life Style, Càncer de pàncrees, METAANALYSIS, Neoplasm Staging, Proportional Hazards Models, Cancer prevention, Science & Technology, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, MORTALITY, CONSUMPTION, medicine.disease, Surgery, Pancreatic Neoplasms, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Nutrition Assessment, PATTERNS, business, 1112 Oncology And Carcinogenesis, Follow-Up Studies
Abstract: Source at http://doi.org/10.1038/bjc.2017.14 British Journal of Cancer 2017, 116:811–820 Background: The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs). Results: Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs low adherence¼0.99; 95% CI: 0.77–1.26, and HR per increments of two units in adherence to arMED¼1.00; 95% CI: 0.94–1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern. Conclusions: A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.
Published: 2017

36. Smoking and Long-Term Risk of Type 2 Diabetes:The EPIC-InterAct Study in European Populations

Author: M. Luisa Redondo, Stephen J. Sharp, Salvatore Panico, Anne Tjønneland, Blandine de Lauzon-Guillain, Antonio Agudo, Olov Rolandsson, Domenico Palli, Nita G. Forouhi, Joline W.J. Beulens, Kim Overvad, Timothy J. Key, Elio Riboli, José María Huerta, Yvonne T. van der Schouw, Eva Ardanaz, Birgit Teucher, María José Sánchez, Diana Gavrila, Peter M. Nilsson, Daphne L. van der A, Larraitz Arriola, Guy Fagherazzi, Sara Grioni, Annemieke M.W. Spijkerman, Edith J. M. Feskens, Rosario Tumino, Matthias B. Schulze, Beverley Balkau, Rudolf Kaaks, Claudia Langenberg, Nicholas J. Wareham, Nina Roswall, Carlotta Sacerdote, Nadia Slimani, Paul W. Franks, Heiner Boeing, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, Spijkerman, Annemieke M. W, van der A, Daphne L, Nilsson, Peter M, Ardanaz, Eva, Gavrila, Diana, Agudo, Antonio, Arriola, Larraitz, Balkau, Beverley, Beulens, Joline W, Boeing, Heiner, de Lauzon Guillain, Blandine, Fagherazzi, Guy, Feskens, Edith J. M, Franks, Paul W, Grioni, Sara, Huerta, José María, Kaaks, Rudolf, Key, Timothy J, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Redondo, M. Luisa, Rolandsson, Olov, Roswall, Nina, Sacerdote, Carlotta, Sánchez, María José, Schulze, Matthias B, Slimani, Nadia, Teucher, Birgit, Tjonneland, Anne, Tumino, Rosario, van der Schouw, Yvonne T, Langenberg, Claudia, Sharp, Stephen J, Forouhi, Nita G, Riboli, Elio, and Wareham, Nicholas J.
Subjects: Research design, Gerontology, Male, Nutrition and Disease, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, middle-aged men, Type 2 diabetes, Risk Factors, Neoplasms, Voeding en Ziekte, glucose, physical-activity, Adiposity, Incidence, Hazard ratio, Smoking, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, fat distribution, Female, women, Human, Adult, kora s4/f4 cohort, Follow-Up Studie, insulin-resistance, Diabetes mellitus, active smoking, Internal Medicine, medicine, Humans, Obesity, Risk factor, Aged, VLAG, Advanced and Specialized Nursing, Global Nutrition, Wereldvoeding, business.industry, cigarette-smoking, Risk Factor, Feeding Behavior, Former Smoker, medicine.disease, Diabetes Mellitus, Type 2, Food Habit, Smoking cessation, Neoplasm, business, Demography, Follow-Up Studies, mellitus
Abstract: OBJECTIVE The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors. RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes. RESULTS In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity. CONCLUSIONS Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention.
Published: 2014

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