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1. Prediction of acute myeloid leukaemia risk in healthy individuals.

Author: Abelson, Sagi, Collord, Grace, Ng, Stanley WK, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, McPherson, John D, Johansson, Mattias, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean CY, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, McKay, James, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amos, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, and Shlush, Liran I
Subjects: Humans, Disease Progression, Genetic Predisposition to Disease, Prevalence, Risk Assessment, Age Factors, Mutagenesis, Mutation, Models, Genetic, Adult, Aged, Middle Aged, Health, Female, Male, Leukemia, Myeloid, Acute, Electronic Health Records, Models, Genetic, Leukemia, Myeloid, Acute, General Science & Technology
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
Published: 2018

2. 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

3. Main nutrient patterns are associated with prospective weight change in adults from 10 European countries

Author: Freisling, Heinz, Pisa, Pedro T, Ferrari, Pietro, Byrnes, Graham, Moskal, Aurelie, Dahm, Christina C, Vergnaud, Anne-Claire, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Cadeau, Claire, Kühn, Tilman, Neamat-Allah, Jasmine, Buijsse, Brian, Boeing, Heiner, Halkjær, Jytte, Tjonneland, Anne, Hansen, Camilla P, Quirós, J Ramón, Travier, Noémie, Molina-Montes, Esther, Amiano, Pilar, Huerta, José M, Barricarte, Aurelio, Khaw, Kay-Tee, Wareham, Nicholas, Key, Tim J, Romaguera, Dora, Lu, Yunxia, Lassale, Camille M, Naska, Androniki, Orfanos, Philippos, Trichopoulou, Antonia, Masala, Giovanna, Pala, Valeria, Berrino, Franco, Tumino, Rosario, Ricceri, Fulvio, de Magistris, Maria Santucci, Bueno-de-Mesquita, H Bas, Ocké, Marga C, Sonestedt, Emily, Ericson, Ulrika, Johansson, Mattias, Skeie, Guri, Weiderpass, Elisabete, Braaten, Tonje, Peeters, Petra HM, and Slimani, Nadia
Subjects: Public Health, Biomedical and Clinical Sciences, Nutrition and Dietetics, Health Sciences, Clinical Research, Prevention, Nutrition, Metabolic and endocrine, Adult, Aged, Ascorbic Acid, Calcium, Dietary, Diet, Dietary Fiber, Dietary Proteins, Europe, Female, Folic Acid, Follow-Up Studies, Humans, Linear Models, Male, Middle Aged, Nutrition Assessment, Phosphorus, Dietary, Prospective Studies, Riboflavin, Surveys and Questionnaires, Weight Gain, beta Carotene, Dietary patterns, Energy balance, Nutrients, Obesity, Public health, Weight gain, Nutrition & Dietetics, Nutrition and dietetics, Epidemiology
Abstract: PurposeVarious food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.MethodsThis study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.ResultsMean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.ConclusionsWe identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.
Published: 2016

4. 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

5. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

Author: Steffen, Annika, Huerta, José-Maria, Weiderpass, Elisabete, Bueno-de-Mesquita, HB As, May, Anne M, Siersema, Peter D, Kaaks, Rudolf, Neamat-Allah, Jasmine, Pala, Valeria, Panico, Salvatore, Saieva, Calogero, Tumino, Rosario, Naccarati, Alessio, Dorronsoro, Miren, Sánchez-Cantalejo, Emilio, Ardanaz, Eva, Quirós, J Ramón, Ohlsson, Bodil, Johansson, Mattias, Wallner, Bengt, Overvad, Kim, Halkjaer, Jytte, Tjønneland, Anne, Fagherazzi, Guy, Racine, Antoine, Clavel-Chapelon, Françoise, Key, Tim J, Khaw, Kay-Tee, Wareham, Nick, Lagiou, Pagona, Bamia, Christina, Trichopoulou, Antonia, Ferrari, Pietro, Freisling, Heinz, Lu, Yunxia, Riboli, Elio, Cross, Amanda J, Gonzalez, Carlos A, and Boeing, Heiner
Subjects: Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Rare Diseases, Digestive Diseases, Cancer, Obesity, Nutrition, Adenocarcinoma, Adult, Aged, Body Mass Index, Body Weights and Measures, Esophageal Neoplasms, Europe, Female, Follow-Up Studies, Humans, Male, Middle Aged, Obesity, Abdominal, Population Surveillance, Prospective Studies, Risk, Risk Factors, Stomach Neoplasms, abdominal obesity, body mass index, esophageal cancer, gastric cancer, general obesity, waist circumference, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.
Published: 2015

6. 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
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7. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

Author: Yiallouros, Panayiotis K., Escobedo-de la Peña, Jorge, Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M., Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, James, Bilano, Ver, Stevens, Gretchen A., Cowan, Melanie J., Riley, Leanne M., Chen, Zhengming, Hambleton, Ian R., Jackson, Rod T., Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K., Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A., Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Ängquist, Lars H., Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assunção, Maria Cecília F., Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R., Barbagallo, Carlo M., Barceló, Alberto, Barkat, Amina, Barros, Aluisio J. D., Barros, Mauro V., Bata, Iqbal, Batieha, Anwar M., Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Romdhane, Habiba Ben, Benet, Mikhail, Benson, Lowell S., Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bi, Yufang, Bikbov, Mukharram, Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Björkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bongard, Vanina, Borchini, Rossana, Bovet, Pascal, Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M., Bruno, Graziella, Bueno-de-Mesquita, H. B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., Cruz, Juan J., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abbas, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Do, Ha T. 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Gabriele, Naidu, Balkish M, Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K, Nangia, Vinay B, Narake, Sameer, Nauck, Matthia, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nguyen, Quang V, Nieto-Martínez, Ramfis E, Niiranen, Teemu J, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Parnell, Winsome R, Parsaeian, Mahboubeh, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Peeters, Petra H, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L P, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F, Puder, Jardena J, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A, Redon, Josep, Reganit, Paul Ferdinand M, Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F, Ritti-Dias, Raphael M, Robinson, Sian M, Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S, Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A, Santos, Ina S, Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savva, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C, Snijder, Marieke B, So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I A, Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Shyong Tai, E, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Matie, Traissac, Pierre, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh T H, Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E, Ulmer, Hanno, Uusitalo, Hannu M T, Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M, van Valkengoed, Irene G M, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lar, Vega, Toma, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W M, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N, Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Wedderkopp, Niel, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Emmanuel A, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Justin Y Y, Wong, Tien Yin, Woo, Jean, Giwercman Wu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K, Yoshihara, Akihiro, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad Ali, Zambon, Sabina, Zampelas, Antoni, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, Cisneros, Julio Zuñiga, The State Key Laboratory of Cell Biology [Shanghai, China] (CAS Center for Excellence in Molecular Cell Science), Shanghai Institute of Biochemistry and Cell Biology [Shanghai, China]-University of Chinese Academy of Sciences [Shanghai, China], Imperial College London, University of Kentucky, Middlesex University, Cleveland Clinic, Universidad Peruana Cayetano Heredia (UPCH), Brandeis University, Mulago Hospital [Kampala, Ouganda], Department of Epidemiology and Public Health, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organisation (WHO), Al-Quds University, Discipline of Medicine, University of South Australia [Adelaide], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Centre for Industrial Management, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Preventive Medicine, Copenhagen University Hospitals, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Dept. Atherosclerose, University of Iceland [Reykjavik], Institute for Biotechnology and Bioengineering (IBB), Technical University of Lisbon, Medical University of Łódź (MUL), Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid (UAM), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Sunder Lal Jain Hospital, Ufa Eye Research Institute [Bashkortostan], National Institute of Public Health, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, CHU Toulouse [Toulouse], Institute of Social and Preventive Medicine, Lausanne university hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), ASU - School for Engineering of Matter, Transport and Energy, Arizona State University [Tempe] (ASU), Universidade do Porto = University of Porto, University of Oxford [Oxford], Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), 2nd Department of Internal Medicine, Molecular Medicine, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-IRC KULAK, Department of Public Health, State University of Ghent, MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, Réseau International des Instituts Pasteur (RIIP), Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Sahlgrenska University Hospital [Gothenburg], Institute of Metabolic Science, MRC, Institut National de Nutrition et de Technologie Alimentaire (INNTA), University of Huddersfield, IMIM-Hospital del Mar, Generalitat de Catalunya, Medstar Research Institute, Queen's University [Belfast] (QUB), Medical Research Council, Applied Sciences, National Research Institute on Food and Nutrition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Innsbruck Medical University [Austria] (IMU), Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Laboratoire d'Etude des Mammifères Marins (LEMM), Océanopolis [Brest], Faculté de Médecine Henri Warembourg - Université de Lille, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Centro Investig Quim Aplicada, Coahuila, Mexico, Centro Investigacion en Quimica Aplicada, Coahuila, Mexico, University of Geneva [Switzerland], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], Health Services Research Unit, Danish Cancer Society, Institute of Cancer Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), University College of London [London] (UCL), The Georges Institute for International Health, The University of Sydney, School of Information Technology, Deakin University Waurn Ponds, Faculté de Médecine, Université Djilali Liabès [Sidi-Bel-Abbès], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), VU University Medical Center [Amsterdam], Universiteit Gent = Ghent University [Belgium] (UGENT), Faculty of Agricultural and Food Science, American University of Beirut [Beyrouth] (AUB), Åbo Akademi University [Turku], Department of Public Health Sciences, Karolinska Institutet [Stockholm], Great Lakes Institute for Environmental Research, University of Windsor [Ca], Universität Heidelberg [Heidelberg], Research Center for Prevention and Health, University of Ljubljana, Division of Cancer Epidemiology, University of Crete School of medicine, School of Public Health and Clinical Nutrition, University of Eastern Finland, Institute of Epidemiology and Social Medicine, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms-Universität Bonn, Cancer Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Oncology, University of Tampere Medical School, University of Tampere, Wageningen University and Research [Wageningen] (WUR), Centre for Environmental Health, National Institue of Public Health, School of Public Health, The University of Hong Kong (HKU), Tehran University of Medical Sciences, Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN), INRAN, National University of Singapore (NUS), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Uppsala Universitet [Uppsala], Department of Public Health and Community Medicine, University of Gothenburg (GU), Institute of Earthquake Science, CEA, Beijing, CEA, Beijing, University of Porto Medical School, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aging Program, National research council, Padua, Italy, Baker IDI Heart and Diabetes Institute, Institute of Internal Medicine, Russian Academy of Medical Sciences, Department of Nutrition and Dietetics, Harokopio University, Emory University [Atlanta, GA], Départment of Biotechnology, Faculty of Science, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tartu, Department of Community, Université Ain Shams-Faculty of Medicine-Environmental and Occupational Medicine, Pécsi Tudemányegyetem, Department of Community, Environmental and Occupational Medicine, Université Ain Shams, Research Centre in Physical Activity, Health and Leisure, Nutrition and Metabolism Section, International Agency for Research on Cancer, Bushehr University of Medical Sciences, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Università degli studi di Palermo - University of Palermo, MRc Environmental Epidemiology Unit, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Department of Epidemiology and Population Studies, Jagiellonian University, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Social Robotics Laboratory, University of Freiburg, Freiburg im Breisgau, Department of Ophthalmology, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, University of Bari Aldo Moro (UNIBA), Department of Cardiology, Eastbourne General Hospital, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), King‘s College London, Public Health Sciences, University of Edinburgh, Movement Disorders and Tourette Centre, Genetica medicala, Victor Babeş University of Medicine and Pharmacy (UMFT), Andrology Unit, United Laboratories of Tartu University Clinics, Tampere University Hospital, Department of Hygiene and Epidemiology, Dept of Epidemiology and Public Health, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Institut de Veille Sanitaire (INVS), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], University of São Paulo (USP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Department of Reproductive Endocrinology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Central Hospital and Faculty of medicine and biomedical sciences university, University of Yaoundé [Cameroun], Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, School of Computing [Leeds], University of Leeds, Copenhagen University Hospital, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Applied Food Science, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, University of Amsterdam, Dept. of Social Medecine, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Africa Centre for Health and Population Studies, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Center for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Department of Cardiovascular Sciences [Leuven], Cancer Epidemiology Institute, Department of Epidemiology and Health Promotion (MONICA Data Centre), National Public Health Institute, Nutrition et Alimentation des Populations aux Suds (NutriPass), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Havard School of Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], University of Kuopio, Tampere University, University Medical Centre Utrecht, Department of Social Medicine, Amsterdam, Center for Metabolic Bone Diseases, Catholic University of Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Universidad Miguel Hernández [Elche] (UMH), Institute of Public Health and Clinical Nutrition [Kuopio, Finland], Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Community Health Sciences, St George's University of London, Medizinische Universität Wien = Medical University of Vienna, Medical University of Silesia (SUM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Innsbruck, National Institute of Hygiene Warsaw, Johns Hopkins University School of Medicine [Baltimore], Food Science and Technology, Beijing Forestry University, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics (CAE-NUAA), NUAA, Chinese Center for Disease Control and Prevention, Department of Applied Mathematics, School of Science, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, Siemens Corporate Research, Siemens AG [Munich], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), This work was supported by the Wellcome Trust [101506/Z/13/Z]., NCD Risk Factor Collaboration (NCD-RisC). We thank WHO country and regional offices and the World Heart Federation for support in data identification and access., Universidad Autonoma de Madrid (UAM), University of Turin, Universidade do Porto, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Lille 2 - Faculté de Médecine, Westfälische Wilhelms-Universität Münster (WWU), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Lund University Diabetes Centre-Lund University [Lund], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Medical University of Silesia, Katowice, Apollo - University of Cambridge Repository, University of Kentucky (UK), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lausanne University Hospital, University of Oxford, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université de Genève = University of Geneva (UNIGE), Deakin University [Waurn Ponds], Universiteit Gent = Ghent University (UGENT), Universität Heidelberg [Heidelberg] = Heidelberg University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Universidade de São Paulo = University of São Paulo (USP), Lund University [Lund], Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Yiallouros, Panayiotis K. [0000-0002-8339-9285], Giampaoli, Simona [0000-0002-6679-1488], Moschonis, George [0000-0003-3009-6675], Papandreou, Dimitrios [0000-0002-4923-484X], Stathopoulou, Maria G. [0000-0003-4376-2083], Stergiou, George S. [0000-0002-6132-0038], Trichopoulou, Antonia [0000-0002-7204-6396], Valvi, Damaskini [0000-0003-4633-229X], Chen, Z, Woodward, M, Key, T, and Smith, M
Subjects: systolic blood pressure, Settore MED/09 - Medicina Interna, blood pressure measurement, HEALTH EXAMINATION SURVEYS, Blood Pressure, Hypertension, Population Health, Global Health, Non-communicable Disease, Epidemiology, [SDV]Life Sciences [q-bio], global health, South Asia, purl.org/pe-repo/ocde/ford#3.03.09 [https], kohonnut verenpaine, Medicine and Health Sciences, middle income country, measurement method, skin and connective tissue diseases, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771, Public, Environmental & Occupational Health, adult, Population health, public health, blood pressure regulation, Public Health, Global Health, Social Medicine and Epidemiology, Non-communicable disease, kansainvälinen vertailu, health survey, aged, female, priority journal, Blood pressure, mean arterial pressure, GLOBAL TRENDS, SODIUM-INTAKE, Life Sciences & Biomedicine, survey design, hypertension, prevalence, Global health, UNITED-STATES, URBAN COMMUNITIES, Article, SECULAR TRENDS, Middle East, Central Asia, male, disease prevalence, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, kansanterveys, blood, SYSTEMATIC ANALYSIS, human, verenpainetauti, non-communicable disease, Science & Technology, Pacific Ocean, high income country, diastolic blood pressure, Pacific Rim, Blood Pressure - Epidemiology - Population, North Africa, major clinical study, HYPERTENSION PREVALENCE, verenpaine, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, ARTERIAL-HYPERTENSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, POTASSIUM INTAKE, sense organs, trend analysis, trend study, population research, population health, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, low income country
Abstract: Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups., This work was supported by the Wellcome Trust [101506/Z/13/Z].
Published: 2018
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8. 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

9. 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
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10. 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

11. 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
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12. Hepcidin levels and gastric cancer risk in the EPIC-EurGast study

Author: Jakszyn, Paula, Fonseca-Nunes, Ana, Lujan-Barroso, Leila, Aranda, Núria, Tous, Mónica, Arija, Victoria, Cross, Amanda, Bueno-de-Mesquita, H B As, Weiderpass, Elisabete, Kühn, Tilman, Kaaks, Rudolf, Sjöberg, Klas, Ohlsson, Bodil, Tumino, Rosario, Palli, Domenico, Ricceri, Fulvio, Fasanelli, Francesca, Krogh, Vittorio, Mattiello, Amalia, Jenab, Mazda, Gunter, Marc, Perez-Cornago, Aurora, Khaw, Kay-Tee, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Trichopoulou, Antonia, Peppa, Eleni, Vasilopoulou, Effie, Boeing, Heiner, Sánchez-Cantalejo, Emilio, Huerta, José María, Dorronsoro, Miren, Barricarte, Aurelio, Quirós, José Maria, Peeters, Petra H, Agudo, Antonio, and Universitat de Barcelona
Subjects: Male, Cancer Research, Homeòstasi, Adenocarcinoma, hepcidin, iron homeostasis, gastric cancer, cohort study, Mass Spectrometry, Cohort Studies, INFLAMMATION, Hepcidins, Aparell digestiu, Risk Factors, Stomach Neoplasms, hemic and lymphatic diseases, HYPOFERREMIA, Odds Ratio, Journal Article, Humans, Homeostasis, Oncology & Carcinogenesis, Càncer, Cancer, Medicine(all), Science & Technology, nutritional and metabolic diseases, IRON-METABOLISM, Digestive organs, Oncology, Case-Control Studies, Ferritins, Female, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, SERUM HEPCIDIN, Chromatography, Liquid
Abstract: Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5ng/l = 0.96, 95% CI = 0.93-0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a non-significant 38% (95% CI: -69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis. This article is protected by copyright. All rights reserved.
Published: 2017
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13. 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
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14. 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
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15. 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
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16. 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
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17. 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.

18. 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.

19. 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.

20. 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

21. Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition

Author: Schmidt, Julie A, Fensom, Georgina K, Rinaldi, Sabina, Scalbert, Augustin, Appleby, Paul N, Achaintre, David, Gicquiau, Audrey, Gunter, Marc J, Ferrari, Pietro, Kaaks, Rudolf, Kühn, Tilman, Floegel, Anna, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Anifantis, Eleutherios, Agnoli, Claudia, Palli, Domenico, Trevisan, Morena, Tumino, Rosario, Bueno-De-Mesquita, H Bas, Agudo, Antonio, Larrañaga, Nerea, Redondo-Sánchez, Daniel, Barricarte, Aurelio, Huerta, José Maria, Quirós, J Ramón, Wareham, Nick, Khaw, Kay-Tee, Perez-Cornago, Aurora, Johansson, Mattias, Cross, Amanda J, Tsilidis, Konstantinos K, Riboli, Elio, Key, Timothy J, and Travis, Ruth C
Subjects: Male, Sphingolipids, Mass spectrometry, Biogenic amines, Nutritional Status, Prostatic Neoplasms, European Prospective Investigation into Cancer and Nutrition (EPIC), Glycerophospholipids, Prostate cancer risk, Middle Aged, 3. Good health, Cohort Studies, Logistic Models, Hexose, Case-Control Studies, Odds Ratio, Amino acids, Metabolomics, Humans, Prospective Studies, Prospective study, Biomarkers, Acylcarnitines, Aged, Follow-Up Studies
Abstract: BACKGROUND: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. RESULTS: Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR1SD) = 0.73; 95% confidence interval (CI) 0.62-0.86; p trend = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR1SD = 0.54; 95% CI 0.40-0.72; p trend = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4. CONCLUSIONS: Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.

22. Prediction of acute myeloid leukaemia risk in healthy individuals

Author: Abelson, Sagi, Collord, Grace, Ng, Stanley WK, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, McPherson, John D, Johansson, Mattias, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean CY, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, McKay, James, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amos, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, and Shlush, Liran I
Subjects: Adult, Male, Models, Genetic, Age Factors, Middle Aged, Risk Assessment, 3. Good health, Leukemia, Myeloid, Acute, Health, Mutagenesis, hemic and lymphatic diseases, Mutation, Disease Progression, Prevalence, Electronic Health Records, Humans, Female, Genetic Predisposition to Disease, neoplasms, Aged
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.

23. 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.

24. 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.

25. 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.

26. Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study

Author: Murphy, Neil, Ward, Heather A, Jenab, Mazda, Rothwell, Joseph A, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Kvaskoff, Marina, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Aleksandrova, Krasimira, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Tjønneland, Anne, Kyrø, Cecilie, Overvad, Kim, Dahm, Christina C, Jakszyn, Paula, Sánchez, Maria-Jose, Gil, Leire, Huerta, José M, Barricarte, Aurelio, Quirós, J Ramón, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-De-Mesquita, Bas, Peeters, Petra H, Gylling, Björn, Myte, Robin, Jirström, Karin, Berntsson, Jonna, Xue, Xiaonan, Riboli, Elio, Cross, Amanda J, and Gunter, Marc J
Subjects: 2. Zero hunger, Colorectal Cancer, Adult, Male, Alcohol Drinking, Colon, Incidence, Smoking, Rectum, Colonoscopy, Proximal Colon, Middle Aged, 3. Good health, Europe, Anatomic Subsite, Risk Factors, Humans, Female, Prospective Studies, Distal Colon, Heterogeneity, Colorectal Neoplasms, Exercise, Life Style, Follow-Up Studies
Abstract: BACKGROUND & AIMS: Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision. METHODS: In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. RESULTS: After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. CONCLUSIONS: The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.

27. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition

Author: Bradbury, Kathryn E, Appleby, Paul N, Tipper, Sarah J, Travis, Ruth C, Allen, Naomi E, Kvaskoff, Marina, Overvad, Kim, Tjønneland, Anne, Halkjaer, Jytte, Cervenka, Iris, Mahamat-Saleh, Yahya, Bonnet, Fabrice, Kaaks, Rudolf, Fortner, Renée T, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Stratigos, Alexander J, Palli, Domenico, Grioni, Sara, Matullo, Giuseppe, Panico, Salvatore, Tumino, Rosario, Peeters, Petra H, Bueno-De-Mesquita, H Bas, Ghiasvand, Reza, Veierød, Marit B, Weiderpass, Elisabete, Bonet, Catalina, Molina, Elena, Huerta, José M, Larrañaga, Nerea, Barricarte, Aurelio, Merino, Susana, Isaksson, Karolin, Stocks, Tanja, Ljuslinder, Ingrid, Hemmingsson, Oskar, Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc J, Rinaldi, Sabina, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, and Key, Timothy J
Subjects: Adult, Male, Nutritional Status, Prostatic Neoplasms, Breast Neoplasms, insulin-like growth factor I, Middle Aged, prospective studies, 3. Good health, Europe, Risk Factors, Case-Control Studies, melanoma, Odds Ratio, biomarker, Humans, Female, EPIC, height, Aged
Abstract: Insulin-like growth factor-I (IGF-I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF-I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF-I concentrations and melanoma risk. A nested case-control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF-I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF-I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF-I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF-I measured in adulthood and the risk of melanoma.

28. 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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29. 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
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30. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Author: Angela M Wood, Stephen Kaptoge, Adam S Butterworth, Peter Willeit, Samantha Warnakula, Thomas Bolton, Ellie Paige, Dirk S Paul, Michael Sweeting, Stephen Burgess, Steven Bell, William Astle, David Stevens, Albert Koulman, Randi M Selmer, W M Monique Verschuren, Shinichi Sato, Inger Njølstad, Mark Woodward, Veikko Salomaa, Børge G Nordestgaard, Bu B Yeap, Astrid Fletcher, Olle Melander, Lewis H Kuller, Beverley Balkau, Michael Marmot, Wolfgang Koenig, Edoardo Casiglia, Cyrus Cooper, Volker Arndt, Oscar H Franco, Patrik Wennberg, John Gallacher, Agustín Gómez de la Cámara, Henry Völzke, Christina C Dahm, Caroline E Dale, Manuela M Bergmann, Carlos J Crespo, Yvonne T van der Schouw, Rudolf Kaaks, Leon A Simons, Pagona Lagiou, Josje D Schoufour, Jolanda M A Boer, Timothy J Key, Beatriz Rodriguez, Conchi Moreno-Iribas, Karina W Davidson, James O Taylor, Carlotta Sacerdote, Robert B Wallace, J Ramon Quiros, Rosario Tumino, Dan G Blazer, Allan Linneberg, Makoto Daimon, Salvatore Panico, Barbara Howard, Guri Skeie, Timo Strandberg, Elisabete Weiderpass, Paul J Nietert, Bruce M Psaty, Daan Kromhout, Elena Salamanca-Fernandez, Stefan Kiechl, Harlan M Krumholz, Sara Grioni, Domenico Palli, José M Huerta, Jackie Price, Johan Sundström, Larraitz Arriola, Hisatomi Arima, Ruth C Travis, Demosthenes B Panagiotakos, Anna Karakatsani, Antonia Trichopoulou, Tilman Kühn, Diederick E Grobbee, Elizabeth Barrett-Connor, Natasja van Schoor, Heiner Boeing, Kim Overvad, Jussi Kauhanen, Nick Wareham, Claudia Langenberg, Nita Forouhi, Maria Wennberg, Jean-Pierre Després, Mary Cushman, Jackie A Cooper, Carlos J Rodriguez, Masaru Sakurai, Jonathan E Shaw, Matthew Knuiman, Trudy Voortman, Christa Meisinger, Anne Tjønneland, Hermann Brenner, Luigi Palmieri, Jean Dallongeville, Eric J Brunner, Gerd Assmann, Maurizio Trevisan, Richard F Gillum, Ian Ford, Naveed Sattar, Mariana Lazo, Simon G Thompson, Pietro Ferrari, David A Leon, George Davey Smith, Richard Peto, Rod Jackson, Emily Banks, Emanuele Di Angelantonio, John Danesh, Adam Butterworth, Monique Verschuren, Salomaa Veikko, Astrid Flecther, Manuela Bergmann, Carlos Crespo, Jolanda M.A Boer, J. Ramon Quiros, Eric B Rimm, Dan G Blazer III, Jean-Pierre Dallongeville, Richard F Gillumn, Ian Ford Ford, Simon Thompson, Epidemiology, Wood, Angela M, Kaptoge, Stephen, Butterworth, Adam S, Willeit, Peter, Warnakula, Samantha, Bolton, Thoma, Paige, Ellie, Paul, Dirk S, Sweeting, Michael, Burgess, Stephen, Bell, Steven, Astle, William, Stevens, David, Koulman, Albert, Selmer, Randi M, Verschuren, W M Monique, Sato, Shinichi, Njølstad, Inger, Woodward, Mark, Salomaa, Veikko, Nordestgaard, Børge G, Yeap, Bu B, Fletcher, Astrid, Melander, Olle, Kuller, Lewis H, Balkau, Beverley, Marmot, Michael, Koenig, Wolfgang, Casiglia, Edoardo, Cooper, Cyru, Arndt, Volker, Franco, Oscar H, Wennberg, Patrik, Gallacher, John, de la Cámara, Agustín Gómez, Völzke, Henry, Dahm, Christina C, Dale, Caroline E, Bergmann, Manuela M, Crespo, Carlos J, van der Schouw, Yvonne T, Kaaks, Rudolf, Simons, Leon A, Lagiou, Pagona, Schoufour, Josje D, Boer, Jolanda M A, Key, Timothy J, Rodriguez, Beatriz, Moreno-Iribas, Conchi, Davidson, Karina W, Taylor, James O, Sacerdote, Carlotta, Wallace, Robert B, Quiros, J Ramon, Tumino, Rosario, Blazer, Dan G, Linneberg, Allan, Daimon, Makoto, Panico, Salvatore, Howard, Barbara, Skeie, Guri, Strandberg, Timo, Weiderpass, Elisabete, Nietert, Paul J, Psaty, Bruce M, Kromhout, Daan, Salamanca-Fernandez, Elena, Kiechl, Stefan, Krumholz, Harlan M, Grioni, Sara, Palli, Domenico, Huerta, José M, Price, Jackie, Sundström, Johan, Arriola, Larraitz, Arima, Hisatomi, Travis, Ruth C, Panagiotakos, Demosthenes B, Karakatsani, Anna, Trichopoulou, Antonia, Kühn, Tilman, Grobbee, Diederick E, Barrett-Connor, Elizabeth, van Schoor, Natasja, Boeing, Heiner, Overvad, Kim, Kauhanen, Jussi, Wareham, Nick, Langenberg, Claudia, Forouhi, Nita, Wennberg, Maria, Després, Jean-Pierre, Cushman, Mary, Cooper, Jackie A, Rodriguez, Carlos J, Sakurai, Masaru, Shaw, Jonathan E, Knuiman, Matthew, Voortman, Trudy, Meisinger, Christa, Tjønneland, Anne, Brenner, Hermann, Palmieri, Luigi, Dallongeville, Jean, Brunner, Eric J, Assmann, Gerd, Trevisan, Maurizio, Gillum, Richard F, Ford, Ian, Sattar, Naveed, Lazo, Mariana, Thompson, Simon G, Ferrari, Pietro, Leon, David A, Smith, George Davey, Peto, Richard, Jackson, Rod, Banks, Emily, Di Angelantonio, Emanuele, Danesh, John, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Internal Medicine and Rehabilitation, APH - Personalized Medicine, APH - Aging & Later Life, and Epidemiology and Data Science
Subjects: Male, FLOATING ABSOLUTE RISK, Alcohol abuse, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, Alcohol Drinking/adverse effects, 0302 clinical medicine, Cardiovascular Disease, Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Prospective cohort study, Human Nutrition & Health, media_common, Medicine(all), VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Research Support, Non-U.S. Gov't, Humane Voeding & Gezondheid, Hazard ratio, Substance Abuse, Public Health, Global Health, Social Medicine and Epidemiology, ASSOCIATION, General Medicine, Middle Aged, ddc, 3. Good health, Substance abuse, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, MENDELIAN RANDOMIZATION, Female, Risk assessment, STROKE, Human, Alcohol Drinking, Lower risk, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Research Support, N.I.H., Extramural, US ADULTS, medicine, Journal Article, Life Science, Humans, media_common.cataloged_instance, CORONARY-HEART-DISEASE, ddc:610, Cardiovascular Diseases/etiology, European union, Beroendelära, METAANALYSIS, business.industry, MORTALITY, medicine.disease, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3121 General medicine, internal medicine and other clinical medicine, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Demography
Abstract: BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies.FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively.INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
Published: 2018
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31. Heterogeneity of Colorectal Cancer Risk Factors by Anatomical Subsite in 10 European Countries: A Multinational Cohort Study

Author: Christina C. Dahm, Carlo La Vecchia, Domenico Palli, Salvatore Panico, Nicholas J. Wareham, Amanda J. Cross, Aurelio Barricarte, Jonna Berntsson, Elisabete Weiderpass, Rudolf Kaaks, Mazda Jenab, Anna Karakatsani, Franck Carbonnel, Xiaonan Xue, Heather Ward, Kristin Benjaminsen Borch, Elio Riboli, Marc J. Gunter, Kay-Tee Khaw, Kathryn E. Bradbury, Tilman Kühn, Marina Kvaskoff, Robin Myte, Antonia Trichopoulou, J. Ramón Quirós, Rosario Tumino, Bas Bueno-de-Mesquita, Kim Overvad, Cecilie Kyrø, Sara Grioni, José María Huerta, Francesca Fasanelli, Karin Jirström, Björn Gylling, Leire Gil, Guri Skeie, Neil Murphy, Paula Jakszyn, Marie-Christine Boutron-Ruault, María José Sánchez, Heiner Boeing, Anne Tjønneland, Krasimira Aleksandrova, Petra H.M. Peeters, Joseph A. Rothwell, Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Murphy, Neil, Ward, Heather A, Jenab, Mazda, Rothwell, Joseph A, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Kvaskoff, Marina, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Aleksandrova, Krasimira, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Tjønneland, Anne, Kyrø, Cecilie, Overvad, Kim, Dahm, Christina C, Jakszyn, Paula, Sánchez, Maria-Jose, Gil, Leire, Huerta, José M, Barricarte, Aurelio, Quirós, J Ramón, Khaw, Kay-Tee, Wareham, Nick, Bradbury, Kathryn E, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Fasanelli, Francesca, Panico, Salvatore, Bueno-de-Mesquita, Ba, Peeters, Petra H, Gylling, Björn, Myte, Robin, Jirström, Karin, Berntsson, Jonna, Xue, Xiaonan, Riboli, Elio, Cross, Amanda J, Gunter, Marc J, Department of Medical and Clinical Genetics, Faculty of Medicine, and Imperial College Trust
Subjects: Oncology, Male, Risk Factors, Colorectal cancer, EPIC, Anatomic Subsite, HEIGHT, 0302 clinical medicine, Prospective Studies, 2. Zero hunger, Incidence, Hazard ratio, Smoking, Gastroenterology, Colonoscopy, Proximal Colon, Middle Aged, C-REACTIVE PROTEIN, TIME, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Multinational corporation, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Menopausal hormone therapy, Colorectal Neoplasms, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, Colon, 3122 Cancers, anatomical subsite, Gastroenterology and Hepatology, 03 medical and health sciences, Internal medicine, REGRESSION, Journal Article, medicine, Gastroenterologi, Humans, VDP::Medisinske Fag: 700, Distal Colon, Exercise, Life Style, RECTAL-CANCER, METAANALYSIS, Colorectal Cancer, Cancer och onkologi, Science & Technology, Gastroenterology & Hepatology, Hepatology, business.industry, Risk Factor, Rectum, Cancer, 1103 Clinical Sciences, medicine.disease, VDP::Medical disciplines: 700, PHYSICAL-ACTIVITY, 3121 General medicine, internal medicine and other clinical medicine, Cancer and Oncology, Heterogeneity, business, Follow-Up Studies
Abstract: Background & Aims - Colorectal cancer located at different anatomical subsites may have distinct etiologies and risk factors. Previous studies that have examined this hypothesis have yielded inconsistent results, possibly because most studies have been of insufficient size to identify heterogeneous associations with precision. Methods - In the European Prospective Investigation into Cancer and Nutrition study, we used multivariable joint Cox proportional hazards models, which accounted for tumors at different anatomical sites (proximal colon, distal colon, and rectum) as competing risks, to examine the relationships between 14 established/suspected lifestyle, anthropometric, and reproductive/menstrual risk factors with colorectal cancer risk. Heterogeneity across sites was tested using Wald tests. Results - After a median of 14.9 years of follow-up of 521,330 men and women, 6291 colorectal cancer cases occurred. Physical activity was related inversely to proximal colon and distal colon cancer, but not to rectal cancer (P heterogeneity = .03). Height was associated positively with proximal and distal colon cancer only, but not rectal cancer (P heterogeneity = .0001). For men, but not women, heterogeneous relationships were observed for body mass index (P heterogeneity = .008) and waist circumference (P heterogeneity = .03), with weaker positive associations found for rectal cancer, compared with proximal and distal colon cancer. Current smoking was associated with a greater risk of rectal and proximal colon cancer, but not distal colon cancer (P heterogeneity = .05). No heterogeneity by anatomical site was found for alcohol consumption, diabetes, nonsteroidal anti-inflammatory drug use, and reproductive/menstrual factors. Conclusions - The relationships between physical activity, anthropometry, and smoking with colorectal cancer risk differed by subsite, supporting the hypothesis that tumors in different anatomical regions may have distinct etiologies.
Published: 2019
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32. 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
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33. 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
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34. Circulating insulin-like growth factor I in relation to melanoma risk in the European prospective investigation into cancer and nutrition

Author: Oskar Hemmingsson, Renée T. Fortner, Marit B. Veierød, Catalina Bonet, Marc J. Gunter, Marina Kvaskoff, Sabina Rinaldi, Susana Merino, Aurelio Barricarte, Kim Overvad, Heiner Boeing, Domenico Palli, Dagfinn Aune, Nerea Larrañaga, Timothy J. Key, José María Huerta, H. Bas Bueno-de-Mesquita, Yahya Mahamat-Saleh, Rudolf Kaaks, Iris Cervenka, Konstantinos K. Tsilidis, Kay-Tee Khaw, Alexander J. Stratigos, Sarah Tipper, Ingrid Ljuslinder, Petra H.M. Peeters, Rosario Tumino, Jytte Halkjær, Salvatore Panico, Ruth C. Travis, Fabrice Bonnet, Paul N. Appleby, Giuseppe Matullo, Carlo La Vecchia, Sara Grioni, Nicholas J. Wareham, Elio Riboli, Reza Ghiasvand, Tanja Stocks, Elena Molina, Kathryn E. Bradbury, Naomi E. Allen, Karolin Isaksson, Antonia Trichopoulou, Elisabete Weiderpass, Anne Tjønneland, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Faculty of Medicine, World Cancer Research Fund International, Bradbury, Kathryn E, Appleby, Paul N, Tipper, Sarah J, Travis, Ruth C, Allen, Naomi E, Kvaskoff, Marina, Overvad, Kim, Tjønneland, Anne, Halkjaer, Jytte, Cervenka, Iri, Mahamat-Saleh, Yahya, Bonnet, Fabrice, Kaaks, Rudolf, Fortner, Renée T, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Stratigos, Alexander J, Palli, Domenico, Grioni, Sara, Matullo, Giuseppe, Panico, Salvatore, Tumino, Rosario, Peeters, Petra H, Bueno-de-Mesquita, H Ba, Ghiasvand, Reza, Veierød, Marit B, Weiderpass, Elisabete, Bonet, Catalina, Molina, Elena, Huerta, José M, Larrañaga, Nerea, Barricarte, Aurelio, Merino, Susana, Isaksson, Karolin, Stocks, Tanja, Ljuslinder, Ingrid, Hemmingsson, Oskar, Wareham, Nick, Khaw, Kay-Tee, Gunter, Marc J, Rinaldi, Sabina, Tsilidis, Konstantinos K, Aune, Dagfinn, Riboli, Elio, Key, Timothy J, Bradbury, Kathryn E [0000-0003-3345-7333], Kvaskoff, Marina [0000-0002-4557-3772], La Vecchia, Carlo [0000-0003-1441-897X], Palli, Domenico [0000-0002-5558-2437], Matullo, Giuseppe [0000-0003-0674-7757], Veierød, Marit B [0000-0002-2083-2758], Ljuslinder, Ingrid [0000-0002-5046-1820], Rinaldi, Sabina [0000-0002-6846-1204], and Apollo - University of Cambridge Repository
Subjects: Oncology, Male, Cancer Research, CUTANEOUS MELANOMA, 030207 dermatology & venereal diseases, 0302 clinical medicine, Risk Factors, Insulina, Odds Ratio, Insulin, Prospective cohort study, Càncer, Breast Neoplasms/etiology, INDEX, Cancer, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Melanoma, Melanoma/etiology, insulin-like growth factor I, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, IGF-I, Europe, Insulin-Like Growth Factor I/metabolism, 030220 oncology & carcinogenesis, Cohort, biomarker, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, 3122 Cancers, Nutritional Status, Breast Neoplasms, 03 medical and health sciences, Internal medicine, medicine, Journal Article, melanoma, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Nutrició, METAANALYSIS, Nutrition, Aged, Science & Technology, Nutritional Status/physiology, business.industry, Kirurgi, Case-control study, Prostatic Neoplasms, Odds ratio, medicine.disease, Confidence interval, prospective studies, Prostatic Neoplasms/etiology, Case-Control Studies, Cutaneous melanoma, CELLS, EPIC, height, Surgery, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: Source at https://doi.org/10.1002/ijc.31854. Insulin‐like growth factor‐I (IGF‐I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF‐I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF‐I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF‐I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF‐I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF‐I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF‐I measured in adulthood and the risk of melanoma.
Published: 2018
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35. Prediction of acute myeloid leukaemia risk in healthy individuals

Author: Aurelio Barricarte, Claire Hardy, Kristian M. Bowles, Abigail Britten, Mattias Johansson, Sabina Sieri, Kay-Tee Khaw, Sagi Abelson, Philip A. Beer, Stanley W.K. Ng, Matthieu Foll, Lee Timms, Diana Hoult, Salvatore Panico, Shabina Hayat, Elena Salamanca-Fernández, Paul M. Krzyzanowski, Rosario Tumino, Noam Barda, José María Huerta, Lawrence E. Heisler, Jean C.Y. Wang, Inigo Martincorena, Mark D. Minden, Robert Luben, John E. Dick, Trevor J. Pugh, Sam Behjati, Anna Karakatsani, Philip Awadalla, Carlo La Vecchia, Zhen Zhao, Ruth C. Travis, Iulia Cirlan, Omer Weissbrod, Giovanna Masala, Heiner Boeing, Rui Costa, Elio Riboli, Nicholas J. Wareham, Calli Latimer, Philip C. Zuzarte, David T. Jones, Ting Ting Wang, J. Ramón Quirós, Grace Collord, Peter J. Campbell, Roel Vermeulen, Yogi Sundaravadanam, Elli Papaemmanuil, Antonia Trichopoulou, Ran D. Balicer, James McKay, Alwin Krämer, Jessica Miller, Keiran Raine, Jenna Eagles, Paolo Vineis, Netta Mendelson Cohen, Silvia Polidoro, Scott V. Bratman, Amos Tanay, Moritz Gerstung, George S. Vassiliou, Paul Brennan, Eran Segal, Karen Ng, Rudolf Kaaks, Núria Sala, David Soave, Faridah Mbabaali, Danielle Pasternack, Liran I. Shlush, John Douglas Mcpherson, Elisabeth Niemeyer, One Health Chemisch, dIRAS RA-2, Abelson, Sagi, Collord, Grace, Ng, Stanley W K, Weissbrod, Omer, Mendelson Cohen, Netta, Niemeyer, Elisabeth, Barda, Noam, Zuzarte, Philip C, Heisler, Lawrence, Sundaravadanam, Yogi, Luben, Robert, Hayat, Shabina, Wang, Ting Ting, Zhao, Zhen, Cirlan, Iulia, Pugh, Trevor J, Soave, David, Ng, Karen, Latimer, Calli, Hardy, Claire, Raine, Keiran, Jones, David, Hoult, Diana, Britten, Abigail, Mcpherson, John D, Johansson, Mattia, Mbabaali, Faridah, Eagles, Jenna, Miller, Jessica K, Pasternack, Danielle, Timms, Lee, Krzyzanowski, Paul, Awadalla, Philip, Costa, Rui, Segal, Eran, Bratman, Scott V, Beer, Philip, Behjati, Sam, Martincorena, Inigo, Wang, Jean C Y, Bowles, Kristian M, Quirós, J Ramón, Karakatsani, Anna, La Vecchia, Carlo, Trichopoulou, Antonia, Salamanca-Fernández, Elena, Huerta, José M, Barricarte, Aurelio, Travis, Ruth C, Tumino, Rosario, Masala, Giovanna, Boeing, Heiner, Panico, Salvatore, Kaaks, Rudolf, Krämer, Alwin, Sieri, Sabina, Riboli, Elio, Vineis, Paolo, Foll, Matthieu, Mckay, Jame, Polidoro, Silvia, Sala, Núria, Khaw, Kay-Tee, Vermeulen, Roel, Campbell, Peter J, Papaemmanuil, Elli, Minden, Mark D, Tanay, Amo, Balicer, Ran D, Wareham, Nicholas J, Gerstung, Moritz, Dick, John E, Brennan, Paul, Vassiliou, George S, Shlush, Liran I, Italian Institute for Genomic Medicine IIGM, Collord, Grace [0000-0003-1924-4411], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Vassiliou, George [0000-0003-4337-8022], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Oncology, Myeloid, Male, 0302 clinical medicine, Models, hemic and lymphatic diseases, Prevalence, 2.1 Biological and endogenous factors, Electronic Health Records, Aetiology, Cells, Cultured, Cancer, Pediatric, screening and diagnosis, Multidisciplinary, Leukemia, Incidence (epidemiology), Age Factors, CLONAL HEMATOPOIESIS, Hematology, Middle Aged, CANCER, 3. Good health, Multidisciplinary Sciences, Haematopoiesis, Detection, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Myeloid leukemia, Health, 030220 oncology & carcinogenesis, Cohort, Disease Progression, Science & Technology - Other Topics, Female, Adult, medicine.medical_specialty, Pediatric Cancer, Childhood Leukemia, General Science & Technology, Leucèmia mieloide, MODELS, Acute, Risk Assessment, CLASSIFICATION, Article, 03 medical and health sciences, Rare Diseases, Genetic, Cancer stem cell, Internal medicine, MD Multidisciplinary, medicine, Genetics, Mortalitat, Humans, Genetic Predisposition to Disease, Progenitor cell, Mortality, neoplasms, Aged, Science & Technology, Models, Genetic, business.industry, Prevention, SOMATIC MUTATIONS, medicine.disease, EVOLUTION, Hematopoiesis, 4.1 Discovery and preclinical testing of markers and technologies, 030104 developmental biology, Good Health and Well Being, Mutagenesis, Mutation, PATTERNS, Bone marrow, business
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure(1). The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion(2,3). However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)(4-8). Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.
Published: 2018

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

Author: Mattias Johansson, Elena Molina-Portillo, Pietro Ferrari, Rudolf Kaaks, Julie A. Schmidt, Anastasia Kotanidou, Petra H.M. Peeters, Eline H. van Roekel, Augustin Scalbert, Domenico Palli, Khalid Iqbal, Rosario Tumino, Heiner Boeing, José María Huerta, Matty P. Weijenberg, Marie-Christine Boutron-Ruault, Laura Trijsburg, Ruth C. Travis, Fulvio Ricceri, Miren Dorronsoro, Neil Murphy, Antonia Trichopoulou, Agnetha Linn Rostgaard-Hansen, Anne Tjønneland, Anders Håkansson, Sabina Rinaldi, Elio Riboli, Tilman Kühn, J. Ramón Quirós, Leila Lujan-Barroso, Konstantinos K. Tsilidis, Elisabete Weiderpass, Magdalena Stepien, Salvatore Panico, Gianluca Severi, Eva Ardanaz, Bas Bueno-de-Mesquita, Anna Karakatsani, Marion Carayol, Nada Assi, David Achaintre, Mazda Jenab, Kim Overvad, Johan Malm, Marc J. Gunter, Vittorio Krogh, Imperial College Trust, RS: GROW - R1 - Prevention, Epidemiologie, Beleid Economie & Organisatie vd Zorg, van Roekel, Eline H, Trijsburg, Laura, Assi, Nada, Carayol, Marion, Achaintre, David, Murphy, Neil, Rinaldi, Sabina, Schmidt, Julie A, Stepien, Magdalena, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Iqbal, Khalid, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Peeters, Petra H, Bueno-de-Mesquita, Ba, Ardanaz, Eva, Lujan-Barroso, Leila, Quirós, J Ramón, Huerta, José M, Molina-Portillo, Elena, Dorronsoro, Miren, Tsilidis, Konstantinos K, Riboli, Elio, Rostgaard-Hansen, Agnetha Linn, Tjønneland, Anne, Overvad, Kim, Weiderpass, Elisabete, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Trichopoulou, Antonia, Karakatsani, Anna, Kotanidou, Anastasia, Håkansson, Ander, Malm, Johan, Weijenberg, Matty P, Gunter, Marc J, Jenab, Mazda, Johansson, Mattia, Travis, Ruth C, Scalbert, Augustin, and Ferrari, Pietro
Subjects: Male, Metabolite, Physiology, lipid metabolite, Alcohol, Sex Factor, Alcohol Drinking/adverse effects, chemistry.chemical_compound, 0302 clinical medicine, acylcarnitines, Risk Factors, Tandem Mass Spectrometry, Neoplasms, Metabolites, Smoking/adverse effects, Citrulline, targeted metabolomics, Medicine, 030212 general & internal medicine, Prospective Studies, Càncer, Prospective cohort study, Biotransformation, Chromatography, High Pressure Liquid, Cancer, RISK, Chromatography, Nutrition and Dietetics, PLASMA, alcohol, Smoking, targeted metabolomic, VDP::Medical disciplines: 700::Health sciences: 800, Lipid, Middle Aged, Metabòlits, Lipids, FALSE DISCOVERY RATE, APOPTOSIS, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, acylcamitines, VDP::Medisinske Fag: 700::Helsefag: 800, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, High Pressure Liquid, ACID, Neoplasms/blood, Cohort, Consum d'alcohol, POPULATIONS, amino acids, lipid metabolites, Aged, Alcohol Drinking, Biomarkers, Female, Humans, Metabolomics, Self Report, Sex Factors, Life Style, Nutritional Status, Europa, lcsh:Nutrition. Foods and food supply, amino acid, Human, Metabolomic, lcsh:TX341-641, Article, acylcarnitine, 03 medical and health sciences, Metabolomics/methods, SPHINGOMYELINASE, Lipids/blood, business.industry, Risk Factor, CONSUMPTION, Biomarker, Prospective Studie, Metabolic pathway, PHYSICAL-ACTIVITY, chemistry, Neoplasm, 1111 Nutrition And Dietetics, business, Biomarkers/blood, Food Science
Abstract: Source at https://doi.org/10.3390/nu10050654. Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions
Published: 2018
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37. A Prospective Evaluation of Plasma Polyphenol Levels and Colon Cancer Risk

Author: Aurelio Barricarte, Marc J. Gunter, Amanda J. Cross, Eleni Peppa, H. B. Bueno-De-Mesquita, Cecilie Kyrø, Augustin Scalbert, J. Ramón Quirós, Isabelle Savoye, José María Huerta, Tilman Kühn, Heiner Boeing, Marie-Christine Boutron-Ruault, Ingegerd Johansson, Salvatore Panico, Martin Rutegård, Carlotta Sacerdote, Kim Overvad, Kostas Tsilidis, Rosario Tumino, Neil Murphy, Raul Zamora-Ros, Anne Tjønneland, Mazda Jenab, Heinz Freisling, Hwayoung Noh, Aurora Perez-Cornago, María José Sánchez, Franck Carbonnel, Antonia Trichopoulou, David Achaintre, Paolo Vineis, Jone M. Altzibar, Kathryn E. Bradbury, Krasimira Aleksandrova, Sara Grioni, Petra H.M. Peeters, Rudolf Kaaks, Anna Karakatsani, Domenico Palli, Kay-Tee Khaw, Murphy, Neil, Achaintre, David, Zamora-Ros, Raul, Jenab, Mazda, Boutron-Ruault, Marie-Christine, Carbonnel, Franck, Savoye, Isabelle, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Aleksandrova, Krasimira, Tjønneland, Anne, Kyrø, Cecilie, Overvad, Kim, Quirós, J Ramón, Sánchez, Maria-Jose, Altzibar, Jone M, María Huerta, José, Barricarte, Aurelio, Khaw, Kay-Tee, Bradbury, Kathryn E, Perez-Cornago, Aurora, Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Sacerdote, Carlotta, Panico, Salvatore, Bueno-de-Mesquita, H B A, Peeters, Petra H, Rutegård, Martin, Johansson, Ingegerd, Freisling, Heinz, Noh, Hwayoung, Cross, Amanda J, Vineis, Paolo, Tsilidis, Kosta, Gunter, Marc J, and Scalbert, Augustin
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Colorectal cancer, Prospective evaluation, COLORECTAL-CANCER, Body Mass Index, EPIC COHORT, Prostate cancer, chemistry.chemical_compound, 0302 clinical medicine, nested case-control study, Risk Factors, Prospective Studies, Biochemical markers, food and beverages, Biological activity, Equol, Middle Aged, Prognosis, PROSTATE-CANCER, Estudi de casos, colon cancer, 030220 oncology & carcinogenesis, Polifenols, Colonic Neoplasms, Marcadors bioquímics, biomarker, NUTRITION, Female, Life Sciences & Biomedicine, EQUOL, Cancer Epidemiology, FLAVONOID INTAKE, medicine.medical_specialty, ESTROGEN-RECEPTOR-BETA, PHENOL-EXPLORER DATABASE, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Internal medicine, SYSTEMATIC ANALYSIS, medicine, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, METAANALYSIS, Estrogen receptor beta, polyphenols, Cancer och onkologi, Science & Technology, business.industry, biomarkers, nested case–control study, medicine.disease, digestive system diseases, 030104 developmental biology, chemistry, Polyphenol, Case-Control Studies, Cancer and Oncology, Nested case-control study, Case studies, business, EPIC, Follow-Up Studies
Abstract: Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre‐diagnostic plasma polyphenols and colon cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (q values) was computed to control for multiple comparisons. All statistical tests were two‐sided. After false discovery rate correction and in continuous log2‐transformed multivariable models, equol (odds ratio [OR] per log2‐value, 0.86, 95% confidence interval [95% CI] = 0.79–0.93; q value = 0.01) and homovanillic acid (OR per log2‐value, 1.46, 95% CI = 1.16–1.84; q value = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41–0.91, p trend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17–2.53, p trend, What's new? Polyphenols are antioxidants abundant in food, and some polyphenols have demonstrated an anti‐cancer effect. Here, the authors looked for an association between polyphenols and colon cancer risk by conducting a nested case–control analysis within the EPIC cohort. Rather than employing questionnaires that rely on participant memories of their diet, this study directly measured 35 polyphenols in plasma samples and compared them with colon cancer risk. Only 2 chemicals showed any association. Concentrations of equol, which is metabolized from soy foods, were inversely associated with colon cancer risk. Higher levels of homovanillic acid, on the other hand, were associated with increased risk.
Published: 2018
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38. 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
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39. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults

Author: Abarca-GÃ³mez, Leandra, Abdeen, Ziad A, Hamid, Zargar Abdul, Abu-Rmeileh, Niveen M, Acosta-Cazares, Benjamin, Acuin, Cecilia, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A, Agyemang, Charles, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Hazzaa, Hazzaa M, Al-Othman, Amani Rashed, Al-Raddadi, Rajaa, Al Buhairan, Fadia, Al Dhukair, Shahla, Ali, Mohamed M, Ali, Osman, Alkerwi, Ala'a, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A, Andrade, Dolores S, Ã„ngquist, Lars H, Anjana, Ranjit Mohan, Aounallah-Skhiri, Hajer, AraÃºjo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, AssunÃ§Ã£o, Maria CecÃlia F, Aung, May Soe, AvdicovÃ¡, MÃ¡ria, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V, Bahijri, Suhad, Baker, Jennifer L, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, JosÃ© R, Barbagallo, Carlo M, BarcelÃ³, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro VG, Bata, Iqbal, Batieha, Anwar M, Batista, Rosangela L, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Romdhane, Habiba Ben, Benedics, Judith, Benet, Mikhail, Bennett, James E, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bhatti, Zaid, Bhutta, Zulfiqar A, Bi, Hongsheng, Bi, Yufang, Biehl, Anna, Bikbov, Mukharram, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, BjÃ¶rkelund, Cecilia, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M, Boehm, Bernhard O, Boeing, Heiner, Boggia, Jose G, Boissonnet, Carlos P, Bonaccio, Marialaura, Bongard, Vanina, Bovet, Pascal, Braeckevelt, Lien, Braeckman, Lutgart, Bragt, Marjolijn CE, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Breda, JoÃ£o, Brenner, Hermann, Brewster, Lizzy M, Brian, Garry R, Brinduse, Lacramioara, Bruno, Graziella, Bueno-de-Mesquita, H B(as), Bugge, Anna, Buoncristiano, Marta, Burazeri, Genc, Burns, Con, de LeÃ³n, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cama, Tilema, Cameron, Christine, Camolas, JosÃ©, Can, GÃ¼nay, CÃ¢ndido, Ana Paula C, Capanzana, Mario, Capuano, Vincenzo, Cardoso, Viviane C, Carlsson, Axel C, Carvalho, Maria J, Casanueva, Felipe F, Casas, Juan-Pablo, Caserta, Carmelo A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Chetrit, Angela, Chikova-Iscener, Ekaterina, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, MarÃa-Dolores, Cho, Belong, Cho, Yumi, Christensen, Kaare, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Confortin, Susana C, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C, Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L, Crujeiras, Ana B, CUCU, ALEXANDRA, D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Damsgaard, Camilla T, Danaei, Goodarz, Dankner, Rachel, Dantoft, Thomas M, Dastgiri, Saeed, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, De Curtis, Amalia, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, Karin, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, Dehghan, Abbas, Delisle, HÃ©lÃne, Delpeuch, Francis, Deschamps, ValÃ©rie, Dhana, Klodian, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dika, Zivka, Djalalinia, Shirin, Do, Ha TP, Dobson, Annette J, Donati, Maria Benedetta, Donfrancesco, Chiara, Donoso, Silvana P, DÃ¶ring, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, Doua, Kouamelan, Drygas, Wojciech, Duan, Jia Li, Duante, Charmaine, Duleva, Vesselka, Dulskiene, Virginija, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Egbagbe, Eruke E, Eggertsen, Robert, Eiben, Gabriele, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Engle-Stone, Reina, Erasmus, Rajiv T, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, la PeÃ±a, Jorge Escobedo-de, Evans, Alun, Faeh, David, Fall, Caroline H, Sant'Angelo, Victoria Farrugia, Farzadfar, Farshad, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, FernÃ¡ndez-BergÃ©s, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D, Fischer, Krista, Flores, Eric Monterubio, FÃ¶ger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M, Francis, Damian K, Franco, Maria do Carmo, Franco, Oscar H, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Gafencu, Mihai, Galeone, Daniela, Galvano, Fabio, Garcia de la Hera, Manoli, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geiger, Harald, Geleijnse, Johanna M, Ghasemian, Anoosheh, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Giwercman, Aleksander, Godos, Justyna, Gogen, Sibel, Goldsmith, Rebecca A, Goltzman, David, GonÃ§alves, Helen, GonzÃ¡lez-Leon, Margot, GonzÃ¡lez-Rivas, Juan P, Gonzalez-Gross, Marcela, Gottrand, Frederic, GraÃ§a, Antonio Pedro, Graff-Iversen, Sidsel, Grafnetter, DuÅ¡an, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, GrÃ¸ntved, Anders, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Gualdi-Russo, Emanuela, Guallar-CastillÃ³n, Pilar, Guan, Ong Peng, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc, Guo, Xiuhua, Guo, Yin, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Hadjigeorgiou, Charalambos A, Si-Ramlee, Khairil, HalkjÃ¦r, Jytte, Hambleton, Ian R, Hardy, Rebecca, Kumar, Rachakulla Hari, Hassapidou, Maria, Hata, Jun, Hayes, Alison J, He, Jiang, Heidinger-Felso, Regina, Heinen, Mirjam, Hendriks, Marleen Elisabeth, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Herrera, Victor M, Herter-Aeberli, Isabelle, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Hofman, Albert, Hopman, Wilma M, Horimoto, Andrea RVR, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, JosÃ© MarÃa, Petrescu, Constanta Huidumac, Huisman, Martijn, Husseini, Abdullatif, Huu, Chinh Nguyen, Huybrechts, Inge, Hwalla, Nahla, Hyska, Jolanda, Iacoviello, Licia, Iannone, Anna G, Ibarluzea, JesÃºs M, Ibrahim, Mohsen M, Ikeda, Nayu, Ikram, M Arfan, Irazola, Vilma E, Islam, Muhammad, Ismail, Aziz al-Safi, Ivkovic, Vanja, Iwasaki, Masanori, Jackson, Rod T, Jacobs, Jeremy M, Jaddou, Hashem, Jafar, Tazeen, Jamil, Kazi M, Jamrozik, Konrad, Janszky, Imre, Jarani, Juel, Jasienska, Grazyna, Jelakovic, Ana, Jelakovic, Bojan, Jennings, Garry, Jeong, Seung-Lyeal, Jiang, Chao Qiang, JimÃ©nez-Acosta, Santa Magaly, Joffres, Michel, Johansson, Mattias, Jonas, Jost B, JÃ¸rgensen, Torben, Joshi, Pradeep, Jovic, Dragana P, JÃ³zwiak, Jacek, Juolevi, Anne, Jurak, Gregor, JureÅ¡a, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O, Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Kapantais, Efthymios, Karki, Khem B, Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, KeinÃ¤nen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kelleher, Cecily, Kemper, Han CG, Kengne, Andre P, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khang, Young-Ho, Khateeb, Mohammad, Khaw, Kay-Tee, Khouw, Ilse MSL, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klimont, Jeannette, Klumbiene, Jurate, Knoflach, Michael, Koirala, Bhawesh, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kovacs, Viktoria A, Kowlessur, Sudhir, Koziel, Slawomir, Kratzer, Wolfgang, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M, Kulaga, Zbigniew, Kumar, R Krishna, KuneÅ¡ovÃ¡, Marie, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, La, Quang Ngoc, Laamiri, Fatima Zahra, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E, Lauria, Laura, Laxmaiah, Avula, Bao, Khanh Le Nguyen, Le, Tuyen D, Lebanan, May Antonnette O, Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, LehtimÃ¤ki, Terho, LeÃ³n-MuÃ±oz, Luz M, Levitt, Naomi S, Li, Yanping, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lars, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Liu, Jing, Loit, Helle-Mai, Lopes, Luis, Lorbeer, Roberto, Lotufo, Paulo A, Lozano, JosÃ© Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, MA, JUN, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Magriplis, Emmanuella, Mahaletchumy, Alagappan, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia, Manios, Yannis, Mann, Jim I, Manzato, Enzo, Margozzini, Paula, Markaki, Anastasia, Markey, Oonagh, Marques, Larissa P, Marques-Vidal, Pedro, Marrugat, Jaume, Martin-Prevel, Yves, Martin, Rosemarie, Martorell, Reynaldo, Martos, Eva, Marventano, Stefano, Masoodi, Shariq R, Mathiesen, Ellisiv B, Matijasevich, Alicia, Matsha, Tandi E, Mazur, Artur, Mbanya, Jean Claude N, McFarlane, Shelly R, McGarvey, Stephen T, McKee, Martin, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Yusof, Safiah Md, Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisfjord, JÃ¸rgen, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Mensink, Gert BM, Meshram, Indrapal I, Metspalu, Andres, Meyer, Haakon E, Mi, Jie, Michaelsen, Kim F, Michels, Nathalie, Mikkel, Kairit, Miller, Jody C, Minderico, ClÃ¡udia S, Miquel, Juan Francisco, Miranda, J Jaime, Mirkopoulou, Daphne, Mirrakhimov, Erkin, MiÅ¡igoj-Durakovic, Marjeta, Mistretta, Antonio, Mocanu, Veronica, Modesti, Pietro A, Mohamed, Mostafa K, Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Molbo, Drude, MÃ¸llehave, Line T, MÃ¸ller, Niels C, MolnÃ¡r, DÃ©nes, Momenan, Amirabbas, Mondo, Charles K, Monterrubio, Eric A, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Mota-Pinto, Anabela, Motlagh, Mohammad Esmaeel, Motta, Jorge, Mu, Thet Thet, Muc, Magdalena, Muiesan, Maria Lorenza, MÃ¼ller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M, Nakamura, Harunobu, NÃ¡meÅ¡nÃ¡, Jana, Nang, Ei Ei K, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Navarrete-MuÃ±oz, Eva Maria, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-MartÃnez, Ramfis E, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Norat, Teresa, Norie, Sawada, Noto, Davide, Nsour, Mohannad Al, O'Reilly, Dermot, Obreja, Galina, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olafsson, Ã–rn, Olinto, Maria Teresa Anselmo, Oliveira, Isabel O, Oltarzewski, Maciej, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, 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Khateeb, Mohammad, Khaw, Kay-Tee, Khouw, Ilse MSL, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klimont, Jeannette, Klumbiene, Jurate, Knoflach, Michael, Koirala, Bhawesh, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kovacs, Viktoria A, Kowlessur, Sudhir, Koziel, Slawomir, Kratzer, Wolfgang, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M, Kulaga, Zbigniew, Kumar, R Krishna, Kuneå¡ovã¡, Marie, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, Quang Ngoc, La, Laamiri, Fatima Zahra, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E, Lauria, Laura, Laxmaiah, Avula, Bao, Khanh Le Nguyen, Tuyen D, Le, Lebanan, May Antonnette O, Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimã¤ki, Terho, LeÃ³n-MuÃ±oz, Luz M, Levitt, Naomi S, Yanping, Li, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lar, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Liu, Jing, Loit, Helle-Mai, Lopes, Lui, Lorbeer, Roberto, Lotufo, Paulo A, Lozano, JosÃ© Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Guansheng, Ma, Jun, Ma, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Magriplis, Emmanuella, Mahaletchumy, Alagappan, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia, Manios, Yanni, Mann, Jim I, Manzato, Enzo, Margozzini, Paula, Markaki, Anastasia, Markey, Oonagh, Marques, Larissa P, Marques-Vidal, Pedro, Marrugat, Jaume, Martin-Prevel, Yve, Martin, Rosemarie, Martorell, Reynaldo, Martos, Eva, Marventano, Stefano, Masoodi, Shariq R, Mathiesen, Ellisiv B, Matijasevich, Alicia, Matsha, Tandi E, Mazur, Artur, Mbanya, Jean Claude N, Mcfarlane, Shelly R, Mcgarvey, Stephen T, Mckee, Martin, Mclachlan, Stela, Mclean, Rachael M, Mclean, Scott B, Mcnulty, Breige A, Yusof, Safiah Md, Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisfjord, Jã¸rgen, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Mensink, Gert BM, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Jie, Mi, Michaelsen, Kim F, Michels, Nathalie, Mikkel, Kairit, Miller, Jody C, Minderico, ClÃ¡udia S, Miquel, Juan Francisco, Miranda, J Jaime, Mirkopoulou, Daphne, Mirrakhimov, Erkin, MiÅ¡igoj-Durakovic, Marjeta, Mistretta, Antonio, Mocanu, Veronica, Modesti, Pietro A, Mohamed, Mostafa K, Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Molbo, Drude, Mã¸llehave, Line T, Mã¸ller, Niels C, Molnã¡r, Dã©ne, Momenan, Amirabba, Mondo, Charles K, Monterrubio, Eric A, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Mota-Pinto, Anabela, Motlagh, Mohammad Esmaeel, Motta, Jorge, Thet Thet, Mu, Muc, Magdalena, Muiesan, Maria Lorenza, MÃ¼ller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M, Nakamura, Harunobu, Nã¡meå¡nã¡, Jana, Nang, Ei Ei K, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Navarrete-MuÃ±oz, Eva Maria, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-MartÃnez, Ramfis E, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Norat, Teresa, Norie, Sawada, Noto, Davide, Nsour, Mohannad Al, O'Reilly, Dermot, Obreja, Galina, Oda, Eiji, Oehlers, Glenn, Kyungwon, Oh, Ohara, Kumiko, Olafsson, Ã rn, Olinto, Maria Teresa Anselmo, Oliveira, Isabel O, Oltarzewski, Maciej, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Peeters, Petra H, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Perez-Farinos, Napoleon, Pã©rez, Cynthia M, Peters, Annette, Petkeviciene, Janina, Petrauskiene, Ausra, Peykari, Niloofar, Pham, Son Thai, Pierannunzio, Daniela, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Plans-RubiÃ³, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Portegies, Marileen LP, Posch, Georg, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F, Puder, Jardena J, Pudule, Iveta, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rascon-Pacheco, Ramon A, Redon, Josep, Reganit, Paul Ferdinand M, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robinson, Sian M, Robitaille, Cynthia, Rodrigues, Daniela, RodrÃguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, Marãa, RodrÃguez-Villamizar, Laura A, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rã¼hli, Frank J, Ruiz-Betancourt, Blanca Sandra, Russo, Paola, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S, Saidi, Olfa, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerã³n, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, SÃ¡nchez-Abanto, Jose, Sandjaja, Null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Osvaldo, dos Santos, Renata Nune, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Scazufca, Marcia, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Serra-Majem, Lui, Shalnova, Svetlana A, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Shiri, Rahman, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjã¶berg, Agneta, Sjã¶strã¶m, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C, Snijder, Marieke B, Hung-Kwan, So, Sobngwi, Eugãne, Sã¶derberg, Stefan, Soekatri, Moesijanti YE, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sã¸rensen, Thorkild IA, Soric, Maroje, Jã©rome, Charles Sossa, Soumare, Aicha, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Starc, Gregor, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stã¶ckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, SuÃ¡rez-Medina, Ramã³n, Sun, Chien-An, Sundstrã¶m, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Rody G, Sy, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Tautu, Oana-Florentina, Braunerovã¡, Radka TaxovÃ¡, Taylor, Anne, Tchibindat, Fã©licitã©, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, TopÃ³r-Madry, Roman, Tormo, MarÃa JosÃ©, Tornaritis, Michael J, Torrent, Matie, Toselli, Stefania, Traissac, Pierre, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Uusitalo, Hannu MT, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lar, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Vã¶lzke, Henry, Voutilainen, Sari, Vrijheid, Martine, Wade, Alisha N, Wagner, Aline, Waldhã¶r, Thoma, Walton, Janette, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, Wanderley, Rildo S, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Justin YY, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Frederick C, Wu, Jianfeng, Wu, Shouling, Wu, Haiquan, Xu, Liang, Xu, Yamborisut, Uruwan, Yan, Weili, Yang, Xiaoguang, Yardim, Nazan, Xingwang, Ye, Yiallouros, Panayiotis K, Yngve, Agneta, Yoshihara, Akihiro, You, Qi Sheng, Younger-Coleman, Novie O, Yusoff, Faudzi, Yusoff, Muhammad Fadhli M, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zambon, Sabina, Zampelas, Antoni, Zamrazilovã¡, Hana, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, Cisneros, Julio ZuÃ±iga, Bentham, Jame, Di Cesare, Mariachiara, Bilano, Ver, Bixby, Honor, Zhou, Bin, Stevens, Gretchen A, Riley, Leanne M, Taddei, Cristina, Hajifathalian, Kaveh, Yuan, Lu, Savin, Stefan, Cowan, Melanie J, Paciorek, Christopher J, Kengne, Andre Pascal, Zhu, Aubrianna, Ezzati, Majid, Abarca-Gómez, Leandra, Alkerwi, Ala'a, Ängquist, Lars H, Araújo, Joana, Assunção, Maria Cecília F, Avdicová, Mária, Banegas, José R, Barceló, Alberto, Bi, Hongsheng, Bi, Yufang, Björkelund, Cecilia, Bo, Simona, Breda, João, de León, Antonio Cabrera, Camolas, José, Can, Günay, Cândido, Ana Paula C, Chirlaque, María-Dolore, d'Orsi, Eleonora, Delisle, Hélène, Deschamps, Valérie, Do, Ha TP, Döring, Angela, la Peña, Jorge Escobedo-de, Fernández-Bergés, Daniel, Föger, Bernhard, Gonçalves, Helen, González-Leon, Margot, González-Rivas, Juan P, Graça, Antonio Pedro, Grafnetter, Dušan, Grøntved, Ander, Gu, Dongfeng, Guallar-Castillón, Pilar, Halkjær, Jytte, He, Jiang, Ho, Sai Yin, Ho, Suzanne C, Hu, Yonghua, Huerta, José María, Ibarluzea, Jesús M, Jiménez-Acosta, Santa Magaly, Jørgensen, Torben, Józwiak, Jacek, Jureša, Vesna, Keinänen-Kiukaanniemi, Sirkka, Kunešová, Marie, La, Quang Ngoc, Le, Tuyen D, Lehtimäki, Terho, León-Muñoz, Luz M, Li, Yanping, Lozano, José Eugenio, Ma, Guansheng, Ma, Jun, McFarlane, Shelly R, McGarvey, Stephen T, McKee, Martin, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Meisfjord, Jørgen, Mi, Jie, Minderico, Cláudia S, Mišigoj-Durakovic, Marjeta, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Mu, Thet Thet, Müller-Nurasyid, Martina, Námešná, Jana, Navarrete-Muñoz, Eva Maria, Nieto-Martínez, Ramfis E, Oh, Kyungwon, Olafsson, Örn, Pérez, Cynthia M, Plans-Rubió, Pedro, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Rühli, Frank J, Salmerón, Diego, Sánchez-Abanto, Jose, Sandjaja, null, Sjöberg, Agneta, Sjöström, Michael, So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Sørensen, Thorkild IA, Jérome, Charles Sossa, Stöckl, Dori, Suárez-Medina, Ramón, Sundström, Johan, Sy, Rody G, Braunerová, Radka Taxová, Tchibindat, Félicité, Topór-Madry, Roman, Tormo, María José, Völzke, Henry, Waldhör, Thoma, Wu, Frederick C, Wu, Jianfeng, Wu, Shouling, Xu, Haiquan, Xu, Liang, Ye, Xingwang, Zamrazilová, Hana, Cisneros, Julio Zuñiga, and Lu, Yuan
Subjects: Male, obesity, Pediatric Obesity, Settore MED/09 - Medicina Interna, age distribution, Bayes theorem, Niue, [SDV]Life Sciences [q-bio], global health, preschool child, Body Mass Index, underweight, Prevalence, statistics and numerical data, Child, ComputingMilieux_MISCELLANEOUS, Medicine (all), adult, Age Factors, American Samoa, female, priority journal, Child, Preschool, body height, young adult, Cook Islands, Nauru, childhood obesity, Adolescent, Palau, sex difference, Eastern Europe, adolescent obesity, Article, Polynesia, South and Central America, body weight, Federated States of Micronesia, Sex Factors, Thinness, geographic distribution, Humans, controlled study, human, Caribbean, Overweight, North Africa, major clinical study, body mass, United States, purl.org/pe-repo/ocde/ford#3.02.00 [https], age, sex factor, trend study
Abstract: © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground Underweight, overweight, and obesity in childhood and adolescence are associated with adverse health consequences throughout the life-course. Our aim was to estimate worldwide trends in mean body-mass index (BMI) and a comprehensive set of BMI categories that cover underweight to obesity in children and adolescents, and to compare trends with those of adults. Methods We pooled 2416 population-based studies with measurements of height and weight on 128·9 million participants aged 5 years and older, including 31·5 million aged 5–19 years. We used a Bayesian hierarchical model to estimate trends from 1975 to 2016 in 200 countries for mean BMI and for prevalence of BMI in the following categories for children and adolescents aged 5–19 years: more than 2 SD below the median of the WHO growth reference for children and adolescents (referred to as moderate and severe underweight hereafter), 2 SD to more than 1 SD below the median (mild underweight), 1 SD below the median to 1 SD above the median (healthy weight), more than 1 SD to 2 SD above the median (overweight but not obese), and more than 2 SD above the median (obesity). Findings Regional change in age-standardised mean BMI in girls from 1975 to 2016 ranged from virtually no change (−0·01 kg/m2 per decade; 95% credible interval −0·42 to 0·39, posterior probability [PP] of the observed decrease being a true decrease=0·5098) in eastern Europe to an increase of 1·00 kg/m2 per decade (0·69–1·35, PP>0·9999) in central Latin America and an increase of 0·95 kg/m2 per decade (0·64–1·25, PP>0·9999) in Polynesia and Micronesia. The range for boys was from a non-significant increase of 0·09 kg/m2 per decade (−0·33 to 0·49, PP=0·6926) in eastern Europe to an increase of 0·77 kg/m2 per decade (0·50–1·06, PP>0·9999) in Polynesia and Micronesia. Trends in mean BMI have recently flattened in northwestern Europe and the high-income English-speaking and Asia-Pacific regions for both sexes, southwestern Europe for boys, and central and Andean Latin America for girls. By contrast, the rise in BMI has accelerated in east and south Asia for both sexes, and southeast Asia for boys. Global age-standardised prevalence of obesity increased from 0·7% (0·4–1·2) in 1975 to 5·6% (4·8–6·5) in 2016 in girls, and from 0·9% (0·5–1·3) in 1975 to 7·8% (6·7–9·1) in 2016 in boys; the prevalence of moderate and severe underweight decreased from 9·2% (6·0–12·9) in 1975 to 8·4% (6·8–10·1) in 2016 in girls and from 14·8% (10·4–19·5) in 1975 to 12·4% (10·3–14·5) in 2016 in boys. Prevalence of moderate and severe underweight was highest in India, at 22·7% (16·7–29·6) among girls and 30·7% (23·5–38·0) among boys. Prevalence of obesity was more than 30% in girls in Nauru, the Cook Islands, and Palau; and boys in the Cook Islands, Nauru, Palau, Niue, and American Samoa in 2016. Prevalence of obesity was about 20% or more in several countries in Polynesia and Micronesia, the Middle East and north Africa, the Caribbean, and the USA. In 2016, 75 (44–117) million girls and 117 (70–178) million boys worldwide were moderately or severely underweight. In the same year, 50 (24–89) million girls and 74 (39–125) million boys worldwide were obese. Interpretation The rising trends in children's and adolescents' BMI have plateaued in many high-income countries, albeit at high levels, but have accelerated in parts of Asia, with trends no longer correlated with those of adults. Funding Wellcome Trust, AstraZeneca Young Health Programme.
Published: 2017
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40. 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
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41. 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
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42. 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
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43. 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
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44. 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
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45. 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
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46. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

Author: Amanda J. Cross, Petra H.M. Peeters, Pietro Ferrari, Françoise Clavel-Chapelon, Salvatore Panico, Augustin Scalbert, Anja Olsen, José María Huerta, Paolo Vineis, Gianluca Severi, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Bénédicte Elena-Herrmann, Nicholas J. Wareham, Pagona Lagiou, Talita Duarte-Salles, Christina Bamia, Anne Tjønneland, Rudolf Kaaks, Bodil Ohlsson, Magdalena Stepien, Antonio Agudo, Krasimira Aleksandrova, Heiner Boeing, Isabelle Romieu, Kay-Tee Khaw, Veronika Fedirko, Domenico Palli, Julie A. Schmidt, Anne Fages, Rosario Tumino, Valeria Pala, Anna Floegel, Dimitrios Trichopoulos, Miren Dorronsoro, Marc J. Gunter, Klas Sjöberg, Clément Pontoizeau, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Tilman Kühn, Elio Riboli, Mazda Jenab, Antonia Trichopoulou, Esther Molina-Montes, Fages, Anne, Duarte Salles, Talita, Stepien, Magdalena, Ferrari, Pietro, Fedirko, Veronika, Pontoizeau, Clément, Trichopoulou, Antonia, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Clavel Chapelon, Françoise, Boutron Ruault, Marie Christine, Severi, Gianluca, Kaaks, Rudolf, Kuhn, Tilman, Floegel, Anna, Boeing, Heiner, Lagiou, Pagona, Bamia, Christina, Trichopoulos, Dimitrio, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. Ba, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Molina Montes, Esther, Huerta, José María, Ardanaz, Eva, Dorronsoro, Miren, Sjöberg, Kla, Ohlsson, Bodil, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Schmidt, Julie A, Cross, Amanda, Gunter, Marc, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Elena Herrmann, Benedicte, Jenab, Mazda, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ISA - Centre de RMN à très hauts champs, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), parent, International Agency for Cancer Research (IACR), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Institute of Cancer Epidemiology, Danish Cancer Society, Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition, Harvard School of Public Health, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Nutritional Epidemiology Unit, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-IRCCS Foundation, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Community Medicine, University of Tromsø (UiT), Department of Research, Cancer Registry of Norway-Samfundet Folkhälsan, Helsinki, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet [Stockholm], Institut Català d'Oncologia, Spain Institute of Oncology, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Murcia Regional Health Council, Sección de Epidemiología de Enfermedades No Transmisibles, Navarre Public Health Institute, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Volvo, VOLVO-VOLVO, Skane University Hospital [Lund], University of Cambridge School of Clinical Medicine, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford [Oxford], Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Chemistry, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, Biomarkers Group, Nutrition and Metabolism Section, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA, grant number 2009-139, PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), European Research Council (ERC, grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skane and Vasterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 'Civile M. P. Arezzo' Hospital, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), [Fages,A, Pontoizeau,C, Elena-Herrmann,B] Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, Villeurbanne, France. [Duarte-Salles,T, Stepien,M, Ferrari,P, Scalbert,A, Romieu,I, Jenab,M] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Aleksandrova,K, Floegel,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M] INSERM, Centre for Research in Epidemiology and Population Health (CESP), nutrition, Hormones and Women’s Health Team, Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Severi,G, Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Kaaks,R, Kuhn,T] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Bamia,C] Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P, Peeters,PH] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,HB, Cross,A, Gunter,M, RibolI,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Agudo,A] Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Montes,E, Huerta,JM, Ardanaz, E] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Sjöberg,K] Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Travis,RC, Schmidt,JA] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., This work was supported by the French National Cancer Institute (L’Institut National du Cancer, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), University of Naples Federico II = Università degli studi di Napoli Federico II, and University of Oxford
Subjects: Oncology, Male, Neoplasias Hepáticas, Cirrhosis, Magnetic Resonance Spectroscopy, Epidemiology, Hepatocellular carcinoma, Nuclear magnetic resonance, Cohort Studies, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma::Carcinoma, Hepatocellular [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, CIRRHOSIS, Early Detection of Cancer, Medicine(all), 0303 health sciences, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [Medical Subject Headings], Liver Neoplasms, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], Metabolómica, Estudios Prospectivos, General Medicine, Middle Aged, CANCER, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Liver Neoplasm, 030220 oncology & carcinogenesis, Female, Liver cancer, Case-Control Studie, Life Sciences & Biomedicine, Metabolomics, Carcinoma Hepatocelular, Research Article, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], TISSUE METABOLOMICS, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Metabolomic, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus [Medical Subject Headings], Càncer de fetge, 03 medical and health sciences, Medicine, General & Internal, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, IDENTIFY SERUM BIOMARKERS, Internal medicine, General & Internal Medicine, medicine, Humans, Obesity, Epidemiologia, 030304 developmental biology, FATTY LIVER-DISEASE, Aged, Hepatitis, Science & Technology, business.industry, Case-control study, METABONOMICS, Cancer, MASS-SPECTROMETRY, medicine.disease, NMR, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Case-Control Studies, DISCOVERY, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Immunology, RISK-FACTORS, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers. Methods: To address these aspects, an untargeted nuclear magnetic resonance metabolomic approach was applied to pre-diagnostic serum samples obtained from first incident, primary HCC cases (n = 114) and matched controls (n = 222) identified from amongst the participants of a large European prospective cohort. Results: A metabolic pattern associated with HCC risk comprised of perturbations in fatty acid oxidation and amino acid, lipid, and carbohydrate metabolism was observed. Sixteen metabolites of either endogenous or exogenous origin were found to be significantly associated with HCC risk. The influence of hepatitis infection and potential liver damage was assessed, and further analyses were made to distinguish patterns of early or later diagnosis. Conclusion: Our results show clear metabolic alterations from early stages of HCC development with application for better etiologic understanding, prevention, and early detection of this increasingly common cancer., This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA; grant number 2009-139; PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands); European Research Council (ERC; grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).
Published: 2015
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47. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

Author: Steffen, A, Huerta, J-M, Weiderpass, E, Bueno-de-Mesquita, HBA, May, AM, Siersema, PD, Kaaks, R, Neamat-Allah, J, Pala, V, Panico, S, Saieva, C, Tumino, R, Naccarati, A, Dorronsoro, M, Sánchez-Cantalejo, E, Ardanaz, E, Quirós, JR, Ohlsson, B, Johansson, M, Wallner, B, Overvad, K, Halkjaer, J, Tjønneland, A, Fagherazzi, G, Racine, A, Clavel-Chapelon, F, Key, TJ, Khaw, K-T, Wareham, N, Lagiou, P, Bamia, C, Trichopoulou, A, Ferrari, P, Freisling, H, Lu, Y, Riboli, E, Cross, AJ, Gonzalez, CA, Boeing, H, Steffen, Annika, Huerta, José Maria, Weiderpass, Elisabete, Bueno de Mesquita, H. B. A, May, Anne M, Siersema, Peter D, Kaaks, Rudolf, Neamat Allah, Jasmine, Pala, Valeria, Panico, Salvatore, Saieva, Calogero, Tumino, Rosario, Naccarati, Alessio, Dorronsoro, Miren, Sánchez Cantalejo, Emilio, Ardanaz, Eva, Quirós, J. Ramón, Ohlsson, Bodil, Johansson, Mattia, Wallner, Bengt, Overvad, Kim, Halkjaer, Jytte, Tjønneland, Anne, Fagherazzi, Guy, Racine, Antoine, Clavel Chapelon, Françoise, Key, Tim J, Khaw, Kay Tee, Wareham, Nick, Lagiou, Pagona, Bamia, Christina, Trichopoulou, Antonia, Ferrari, Pietro, Freisling, Heinz, Lu, Yunxia, Riboli, Elio, Cross, Amanda J, Gonzalez, Carlos A, and Boeing, Heiner
Subjects: Adult, Male, Risk, Esophageal Neoplasms, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], body mass index, Adenocarcinoma, Follow-Up Studie, abdominal obesity, HELICOBACTER-PYLORI, Risk Factors, Stomach Neoplasms, CARDIA, Journal Article, PARTICIPANTS, Humans, COHORT, Body Weights and Measures, HIP CIRCUMFERENCE, Oncology & Carcinogenesis, Obesity, Prospective Studies, esophageal cancer, Esophageal Neoplasm, METAANALYSIS, Aged, Science & Technology, MORTALITY, Risk Factor, Research Support, Non-U.S. Gov't, gastric cancer, Body Weights and Measure, Middle Aged, waist circumference, BODY-MASS INDEX, Europe, Multicenter Study, Prospective Studie, Oncology, general obesity, Obesity, Abdominal, Population Surveillance, BARRETTS-ESOPHAGUS, ADIPOSITY, Female, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Human, Follow-Up Studies
Abstract: Item does not contain fulltext General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.
Published: 2015
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48. 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
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49. 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
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50. 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
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