title: Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort.
abstract: OBJECTIVE
  The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries.
  
  
  METHODS
  After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95% confidence intervals (HR; 95% CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status).
  
  
  RESULTS
  No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95% CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91% of the cohort artificially sweetened soft drinks increased HCC risk by 6% per 1 serving increment (HR 1.06, 95% CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95% CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95% CI 0.38-0.95; p trend = 0.02 vs. non-consumers).
  
  
  CONCLUSIONS
  Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Stepien
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
authors.forename: Talita
authors.initials: T
authors.lastname: Duarte-Salles
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.|Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.affiliation: Hellenic Health Foundation, Athens, Greece.|Department of Hygiene, Epidemiology, Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Department of Hygiene, Epidemiology, Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.|Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.affiliation: Department of Hygiene, Epidemiology, Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Bamia
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Hansen
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, 94805, Villejuif, France.|University Paris Sud, UMRS 1018, 94805, Villejuif, France.|Institut Gustave Roussy, 94805, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, 94805, Villejuif, France.|University Paris Sud, UMRS 1018, 94805, Villejuif, France.|Institut Gustave Roussy, 94805, Villejuif, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Fagherazzi
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, 3053, Australia.|Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, 3010, Australia.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.affiliation: Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Hellenic Health Foundation, Athens, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Klinaki
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Grioni
authors.affiliation: Dipartamento di Medicina Clinicae Chirurgias, Federico II University, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Cancer Registry and Histopathology Unit, "Civile M.P. Arezzo" Hospital, Ragusa, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Molecular and Genetic Epidemiology Unit, Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.|Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.|The School of Public Health, Imperial College London, London, UK.
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Guri
authors.initials: G
authors.lastname: Skeie
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Research, Cancer Registry of Norway, Oslo, Norway.|Samfundet Folkhälsan, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Parr
authors.affiliation: Public Health Directorate, Asturias, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Quirós
authors.affiliation: Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Buckland
authors.affiliation: Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Molina-Montes
authors.affiliation: Public Health Division of Gipuzkoa, Health Department of Basque Region, BioDonostia Research Institute, San Sebastian, Spain.|CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.|CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.affiliation: CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain.|Navarre Public Health Institute, Pamplona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: Department of Clinical Sciences - Malmö, Lund University, Malmö, Sweden.
authors.forename: Emily
authors.initials: E
authors.lastname: Sonestedt
authors.affiliation: Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.affiliation: Public Health and Clinical Medicine, Nutritional Research, and Arctic Research Center, Umeå University, Umeå, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wennberg
authors.affiliation: Public Health and Clinical Medicine, Nutritional Research, and Arctic Research Center, Umeå University, Umeå, Sweden.
authors.forename: Lena Maria
authors.initials: LM
authors.lastname: Nilsson
authors.affiliation: School of Clinical Medicine, Clinical Gerontology Unit, University of Cambridge, Cambridge, UK.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Bradbury
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Ward
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. jenabm@iarc.fr.
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
mesh_terms: D000368:Aged; D001661:Biliary Tract Neoplasms / Q000453:epidemiology*; D015992:Body Mass Index; D002253:Carbonated Beverages / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D002149:Energy Intake; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D000067030:Fruit and Vegetable Juices; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D064306:Non-Nutritive Sweeteners / Q000008:administration & dosage / Q000009:adverse effects*; D064427:Nutritive Sweeteners / Q000008:administration & dosage / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D044465:White People
chemical_list: D064306:Non-Nutritive Sweeteners; D064427:Nutritive Sweeteners
keywords: Biliary tract cancers; Fruit and vegetable juice; Hepatocellular carcinoma; Prospective cohort; Soft drink