title: Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer.
abstract: Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 µg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 µg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.
authors.affiliation: Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.|Department of Nutrition, Harvard School of Public Health, Boston, MA.
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authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany.
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authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany.
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authors.affiliation: Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
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authors.affiliation: 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.
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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.|Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: H B As
authors.initials: HB
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authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
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authors.affiliation: Hellenic Health Foundation, Athens, Greece.|Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
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authors.affiliation: 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 (IGR), Villejuif, France.
authors.forename: Marie-Christine
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authors.affiliation: 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 (IGR), Villejuif, France.
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authors.affiliation: Hellenic Health Foundation, Athens, Greece.|Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.
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authors.affiliation: Hellenic Health Foundation, Athens, Greece.|Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.|Department of Epidemiology, Harvard School of Public Health, Boston, MA.
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authors.affiliation: Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiologia y Salud Publica-CIBERESP), Spain.|Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
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authors.initials: MD
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authors.forename: José Ramón
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authors.forename: Ruth C
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authors.forename: Kay-Tee
authors.initials: KT
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authors.affiliation: Medical Research Council, Epidemiology Unit, University of Cambridge, United Kingdom.
authors.forename: Nick
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authors.affiliation: Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom.
authors.forename: Elio
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authors.affiliation: Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom.
authors.forename: Marc J
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authors.affiliation: Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
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mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D060749:alpha-2-HS-Glycoprotein / Q000235:genetics / Q000378:metabolism*
chemical_list: C556354:AHSG protein, human; D060749:alpha-2-HS-Glycoprotein
keywords: AHSG; colorectal cancer; fetuin-A