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Int J Cancer. 2015 Aug 15;137(4):911-20. doi: 10.1002/ijc.29448. Epub 2015 Feb 5.

Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer.

Author information

1
Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
2
Department of Nutrition, Harvard School of Public Health, Boston, MA.
3
Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany.
4
Genetics of Allergic Disease Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
5
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
6
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
7
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
8
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
9
Department of Research, Cancer Registry of Norway, Oslo, Norway.
10
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
11
Samfundet Folkhälsan, Helsinki, Finland.
12
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
13
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
14
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
15
Center for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
16
Hellenic Health Foundation, Athens, Greece.
17
Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
18
Danish Cancer Society Research Center, Copenhagen, Denmark.
19
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
20
INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team, Villejuif, France.
21
Université Paris Sud, UMRS, 1018, Villejuif, France.
22
Institut Gustave Roussy (IGR), Villejuif, France.
23
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
24
Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
25
Department of Epidemiology, Harvard School of Public Health, Boston, MA.
26
Human Genetics Foundation (HuGeF), Torino, Italy.
27
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
28
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy.
29
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
30
Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy.
31
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands.
32
Department of Radio Sciences, Oncology, Umeå University, Umea, Sweden.
33
Department of Surgery, Department of Surgical and Perioperative Sciences, Umeå University, Sweden.
34
Department of Clinical Sciences, Lund Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden.
35
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain.
36
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiologia y Salud Publica-CIBERESP), Spain.
37
Navarre Public Health Institute, Pamplona, Spain.
38
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Barcelona, Spain.
39
Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain.
40
Public Health Direction and Biodonostia-Ciberesp, Basque Regional Health Department, San Sebastian, Spain.
41
Public Health Directorate, Asturias, Spain.
42
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
43
Clinical Gerontology, Department of Public Health and Primary care, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
44
Medical Research Council, Epidemiology Unit, University of Cambridge, United Kingdom.
45
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom.

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.

KEYWORDS:

AHSG; colorectal cancer; fetuin-A

PMID:
25611809
DOI:
10.1002/ijc.29448
[Indexed for MEDLINE]
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