title: Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population.
abstract: We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and α-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. Cancer Prev Res; 9(9); 758-65. ©2016 AACR.
authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France. Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Barcelona, Spain.
authors.forename: Talita
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authors.forename: Sandeep
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authors.affiliation: Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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authors.affiliation: Section of Genetics, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
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authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
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authors.affiliation: Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
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authors.affiliation: Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.
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authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy.
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authors.affiliation: Inserm, CESP Centre for Research in Epidemiology and Population Health, U1018, Lifestyle, Genes and Health: Integrative Trans-generational Epidemiology, Villejuif, France. Univ Paris Sud, UMRS 1018, Villejuif, France. Gustave Roussy, Villejuif, France.
authors.forename: Marie-Christine
authors.initials: MC
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
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authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
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authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
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authors.affiliation: Hellenic Health Foundation, Athens, Greece. WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Greece.
authors.forename: Antonia
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authors.affiliation: Hellenic Health Foundation, Athens, Greece. WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Greece.
authors.forename: Pagona
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authors.affiliation: Hellenic Health Foundation, Athens, Greece. WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Greece.
authors.forename: Christina
authors.initials: C
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authors.forename: Domenico
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authors.affiliation: Dipartimento Di Medicina, Clinica E Chirurgia, Federico II University, Naples, Italy.
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authors.affiliation: Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
authors.forename: Rosario
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authors.affiliation: Human Genetics Foundation, Torino Molecular and Genetic Epidemiology Unit, Torino, Italy.
authors.forename: Alessio
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authors.affiliation: 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 Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H B As
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, the Netherlands. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatics, School of Public Health, Imperial College, London, United Kingdom.
authors.forename: Petra H
authors.initials: PH
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authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway. Cancer Registry of Norway, NO-0304 Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Instituet, SE-171 Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, 00250 Helsinki, Finland.
authors.forename: Elisabete
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authors.forename: Antonio
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authors.forename: Emilio
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authors.affiliation: CIBER Epidemiology and Public Health (CIBERESP), Spain. Navarra Public Health Institute, Pamplona, Spain. Navarra Institute for Health Research (IdiSNA) Pamplona, Spain.
authors.forename: Eva
authors.initials: E
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authors.affiliation: CIBER Epidemiology and Public Health (CIBERESP), Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
authors.forename: Diana
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authors.forename: Miren
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authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Mårten
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authors.affiliation: Department of Surgical and Perioperative Sciences, Umeå University, Sweden.
authors.forename: Oskar
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authors.affiliation: Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Bodil
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authors.affiliation: Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden.
authors.forename: Klas
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authors.forename: Kathryn E
authors.initials: KE
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authors.affiliation: Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Elio
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authors.affiliation: Institute for Advanced Biosciences (IAB), Inserm U1209, CNRS UMR5309, Université Grenoble-Alpes, Site Santé Grenoble, Allée des Alpes, La Tronche, France.
authors.forename: Pierre
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000453:epidemiology; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods*; D005060:Europe; D005260:Female; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000097:blood* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D053495:Osteopontin / Q000097:blood*; D012372:ROC Curve; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C506895:SPP1 protein, human; D000509:alpha-Fetoproteins; D053495:Osteopontin