Letter abstract


Nature Genetics 41, 986 - 990 (2009)
Published online: 2 August 2009 | doi:10.1038/ng.429

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

Laufey Amundadottir1,2,55, Peter Kraft3,4,55, Rachael Z Stolzenberg-Solomon2,55, Charles S Fuchs5,6,55, Gloria M Petersen7, Alan A Arslan8,9,10, H Bas Bueno-de-Mesquita11, Myron Gross12, Kathy Helzlsouer13, Eric J Jacobs14, Andrea LaCroix15, Wei Zheng16, Demetrius Albanes2, William Bamlet7, Christine D Berg17, Franco Berrino18, Sheila Bingham19, Julie E Buring20,21, Paige M Bracci22, Federico Canzian23, Françoise Clavel-Chapelon24, Sandra Clipp25, Michelle Cotterchio26, Mariza de Andrade7, Eric J Duell27, John W Fox Jr28, Steven Gallinger29, J Michael Gaziano30, Edward L Giovannucci3,6,31, Michael Goggins32, Carlos A González33, Göran Hallmans34, Susan E Hankinson3,6, Manal Hassan35, Elizabeth A Holly22, David J Hunter3,6, Amy Hutchinson2,36, Rebecca Jackson37, Kevin B Jacobs2,36,38, Mazda Jenab27, Rudolf Kaaks23, Alison P Klein39,40, Charles Kooperberg15, Robert C Kurtz41, Donghui Li35, Shannon M Lynch42, Margaret Mandelson15,43, Robert R McWilliams44, Julie B Mendelsohn2, Dominique S Michaud3,45, Sara H Olson46, Kim Overvad47, Alpa V Patel14, Petra H M Peeters45,48, Aleksandar Rajkovic49, Elio Riboli45, Harvey A Risch50, Xiao-Ou Shu16, Gilles Thomas2, Geoffrey S Tobias2, Dimitrios Trichopoulos3,51, Stephen K Van Den Eeden52, Jarmo Virtamo53, Jean Wactawski-Wende54, Brian M Wolpin5,6, Herbert Yu50, Kai Yu2, Anne Zeleniuch-Jacquotte9,10, Stephen J Chanock1,2,55, Patricia Hartge2,55 & Robert N Hoover2,55

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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 times 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.

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  1. Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
  2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
  3. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
  4. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  6. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  7. Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
  8. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA.
  9. Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.
  10. New York University Cancer Institute, New York, New York, USA.
  11. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, and Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
  12. Department of Laboratory Medicine/Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
  13. Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA.
  14. Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia, USA.
  15. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  16. Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.
  17. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
  18. Etiological Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  19. MRC Dunn Human Nutrition Unit, University of Cambridge, Cambridge, UK.
  20. Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  21. Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA.
  22. Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USA.
  23. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  24. Institut National de la Santé et de la Recherche Médicale (INSERM) and Institut Gustave Roussy, Villejuif, France.
  25. The Johns Hopkins Bloomberg School of Public Health, George W. Comstock Center for Public Health Research and Prevention, Hagerstown, Maryland, USA.
  26. Cancer Care Ontario and Dalla Lana School of Public Health, University of Toronto, Ontario, Canada.
  27. International Agency for Research on Cancer, Lyon, France.
  28. College of Human Medicine, Michigan State University, East Lansing, Michigan, USA.
  29. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
  30. Physicians' Health Study, Divisions of Aging, Cardiovascular Medicine and Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA, and Massachusetts Veterans Epidemiology Research and Information Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA.
  31. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
  32. Departments of Oncology, Pathology and Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  33. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain.
  34. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
  35. Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
  36. Core Genotyping Facility, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.
  37. Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine and Center for Clinical and Translational Science, Ohio State University, Columbus, Ohio, USA.
  38. Bioinformed, LLC, Gaithersburg, Maryland, USA.
  39. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  40. Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, The Sol Goldman Pancreatic Research Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
  41. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  42. Epidemiology 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.
  43. Group Health Center for Health Studies, Seattle, Washington, USA.
  44. Department of Oncology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
  45. Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK.
  46. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
  47. Department of Cardiology and Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark.
  48. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
  49. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA.
  50. Yale University School of Public Health, New Haven, Connecticut, USA.
  51. Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece.
  52. Division of Research, Kaiser Permanente, Northern California Region, Oakland, California, USA.
  53. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  54. Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
  55. These authors contributed equally to this work.

Correspondence to: Stephen J Chanock1,2,55 e-mail: chanocks@mail.nih.gov