Prospective association of liver function biomarkers with development of hepatobiliary cancers

Stepien M 1 , Fedirko V 2 , Duarte-Salles T 1 , Ferrari P 1 , Freisling H 1 , Trepo E 3 Show all authors , Trichopoulou A 4 , Bamia C 5 , Weiderpass E 6 , Olsen A 7 , Tjønneland A 7 , Overvad K 8 , Boutron-Ruault MC 9 , Fagherazzi G 9 , Racine A 9 , Kühn T 10 , Kaaks R 10 , Aleksandrova K 11 , Boeing H 11 , Lagiou P 12 , Benetou V 5 , Trichopoulos D 13 , Palli D 14 , Grioni S 15 , Tumino R 16 , Naccarati A 17 , Panico S 18 , Bueno-de-Mesquita HB 19 , Peeters PH 20 , Lund E 21 , Quirós JR 22 , Nápoles OC 23 , Sánchez MJ 24 , Dorronsoro M 25 , Huerta JM 26 , Ardanaz E 27 , Ohlsson B 28 , Sjöberg K 29 , Werner M 30 , Nystrom H 31 , Khaw KT 32 , Key TJ 33 , Gunter M 34 , Cross A 34 , Riboli E 34 , Romieu I 1 , Jenab M 35

Affiliations 

  • 1 Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France
  • 2 Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA
  • 3 Laboratoire Lyon République, Lyon, France
  • 4 Hellenic Health Foundation, Athens, Greece; Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
  • 5 Hellenic Health Foundation, Athens, Greece; Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
  • 6 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
  • 7 Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
  • 8 Department of Public Health, Section for Epidemiology, Aarhus, Aarhus University, Denmark
  • 9 Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France; Université Paris Sud, UMRS 1018, Villejuif, France; Institut Gustave Roussy, Villejuif, France
  • 10 Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
  • 11 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany
  • 12 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, USA
  • 13 Hellenic Health Foundation, Athens, Greece; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, USA; Hellenic Health Foundation, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
  • 14 Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy
  • 15 Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • 16 Cancer Registry and Histopathology Unit, "Civic-M.P. Arezzo" Hospital, ASP Ragusa, Italy
  • 17 Molecular and Genetic Epidemiology Unit, HuGeF, Human Genetics Foundation, Torino, Italy
  • 18 Dipartamento di Medicina Clinicae Chirurgias, Federico II University, Naples, Italy
  • 19 Dt. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Dt. of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands,; Dt. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom; Dt. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 20 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
  • 21 epartment of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromso, Norway
  • 22 Public Health Directorate, Asturias, Spain
  • 23 Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain
  • 24 Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; CIBER Epidemiology and Public Health-CIBERESP, Spain
  • 25 Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain
  • 26 CIBER Epidemiology and Public Health-CIBERESP, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
  • 27 CIBER Epidemiology and Public Health-CIBERESP, Spain; Navarre Public Health Institute, Pamplona, Spain
  • 28 Department of Clinical Sciences, Division of Internal Medicine, SUS Malmö, Lund University, Malmo, Sweden
  • 29 Department of Clinical Sciences, Division of Internal Medicine, SUS Malmö, Lund University, Malmo, Sweden; Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden
  • 30 Department of Public Health and Clinical Medicine, Umeå University, Umea, Sweden
  • 31 Department of Surgery, Department of Perioperative and Surgical Sciences, Umea University, Umea, Sweden
  • 32 University of Cambridge School of Clinical Medicine, Clinical Gerontology, Cambridge, United Kingdom
  • 33 Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, Oxford, United Kingdom
  • 34 Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, London, United Kingdom
  • 35 Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC-WHO), Lyon, France. Electronic address: jenabm@iarc.fr
Cancer Epidemiol, 2016 Feb;40:179-87.
PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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