Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer

Laufey Amundadottir, Peter Kraft, Rachael Z. Stolzenberg-Solomon, Charles S. Fuchs, Gloria M. Petersen, Alan A. Arslan, H. Bas Bueno-De-Mesquita, Myron Gross, Kathy Helzlsouer, Eric J. Jacobs, Andrea LaCroix, Wei Zheng, Demetrius Albanes, William Bamlet, Christine D. Berg, Franco Berrino, Sheila Bingham, Julie E. Buring, Paige M. Bracci, Federico CanzianFrançoise Clavel-Chapelon, Sandra Clipp, Michelle Cotterchio, Mariza De Andrade, Eric J. Duell, John W. Fox, Steven Gallinger, J. Michael Gaziano, Edward L. Giovannucci, Michael Goggins, Carlos A. González, Göran Hallmans, Susan E. Hankinson, Manal Hassan, Elizabeth A. Holly, David J. Hunter, Amy Hutchinson, Rebecca Jackson, Kevin B. Jacobs, Mazda Jenab, Rudolf Kaaks, Alison P. Klein, Charles Kooperberg, Robert C. Kurtz, Donghui Li, Shannon M. Lynch, Margaret Mandelson, Robert R. McWilliams, Julie B. Mendelsohn, Dominique S. Michaud, Sara H. Olson, Kim Overvad, Alpa V. Patel, Petra H M Peeters, Aleksandar Rajkovic, Elio Riboli, Harvey A. Risch, Xiao Ou Shu, Gilles Thomas, Geoffrey S. Tobias, Dimitrios Trichopoulos, Stephen K. Van Den Eeden, Jarmo Virtamo, Jean Wactawski-Wende, Brian M. Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Stephen J. Chanock, Patricia Hartge, Robert N. Hoover

Research output: Contribution to journalArticlepeer-review

438 Scopus citations

Abstract

We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 × 10-8; multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Original languageEnglish (US)
Pages (from-to)986-990
Number of pages5
JournalNature Genetics
Volume41
Issue number9
DOIs
StatePublished - Sep 2009

Bibliographical note

Funding Information:
34Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. 35Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 36Core Genotyping Facility, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA. 37Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine and Center for Clinical and Translational Science, Ohio State University, Columbus, Ohio, USA. 38Bioinformed, LLC, Gaithersburg, Maryland, USA. 39Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 40Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, The Sol Goldman Pancreatic Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. 41Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 42Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. 43Group Health Center for Health Studies, Seattle, Washington, USA. 44Department of Oncology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA. 45Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK. 46Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. 47Department of Cardiology and Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. 48Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 49Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA. 50Yale University School of Public Health, New Haven, Connecticut, USA. 51Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece. 52Division of Research, Kaiser Permanente, Northern California Region, Oakland, California, USA. 53Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. 54Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA. 55These authors contributed equally to this work. Correspondence should be addressed to S.J.C. (chanocks@mail.nih.gov).

Funding Information:
Study participants. Participants in stage 1 of the GWAS were drawn from 12 cohort studies and one case-control study (Supplementary Table 1) in the Pancreatic Cancer Cohort Consortium Genome-Wide Association Study (Pan-Scan1) and are part of a larger international consortium, the National Cancer Institute–sponsored Cohort Consortium. They include the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (ATBC)8, CLUE II (ref. 10), the American Cancer Society Cancer Prevention Study II (CPS-II)7, the European Prospective Investigation into Cancer and Nutrition (EPIC, comprising cohorts from Denmark, France, Germany, the UK, Greece, Italy, the Netherlands, Spain and Sweden)9, the Health Professionals Follow-up Study (HPFS)11, Nurses’ Health Study (NHS)11, the New York University Women’s Health Study (NYUWHS)12, the Physicians’ Health Study I (PHS I)11, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)13, the Shanghai Men’s and Women’s Health Study (SMWHS)14,15, the Women’s Health Initiative (WHI)16, and the Women’s Health Study (WHS)17. Each cohort that participated in PanScan had a defined population from whom blood or buccal cells were collected before the diagnosis of pancreatic cancer. Incident primary pancreatic adenocarcinoma cases were identified by self-report with subsequent medical record review, linkage with a cancer registry or both. Cases were defined as primary adenocarcinoma of the exocrine pancreas (ICD-O-3 code C250–C259). Non-exocrine pancreatic tumors (histology type 8150, 8151, 8153, 8155 and 8240) were excluded.

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