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

References

  1. Jemal, A. et al. Cancer statistics, 2008. CA Cancer J. Clin. 58, 71–96 (2008).
    Article PubMed Google Scholar
  2. Ferlay, J., Bray, F., Pisani, P. & Parkin, D.M. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5, IARC_Press_, Lyon (2004).
  3. Anderson, K.E., Mack, T. & Silverman, D. Cancer of the pancreas. in Cancer Epidemiology and Prevention (ed. Schottenfeld, D. & Fraumeni, J.J.) (Oxford Univ. Press, New York, 2006).
    Google Scholar
  4. Lowenfels, A.B. et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J. Natl. Cancer Inst. 89, 442–446 (1997).
    Article CAS PubMed Google Scholar
  5. Castleman, B. Case records of the Massachusetts General Hospital. N. Engl. J. Med. 286, 1353–1359 (1972).
    Article Google Scholar
  6. Klein, A.P. et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 64, 2634–2638 (2004).
    Article CAS PubMed Google Scholar
  7. Calle, E.E. et al. The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics. Cancer 94, 2490–2501 (2002).
    Article PubMed Google Scholar
  8. The ATBC Cancer Prevention Study Group. The alpha-tocopherol, beta-carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Ann. Epidemiol. 4, 1–10 (1994).
  9. Riboli, E. et al. European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr. 5, 1113–1124 (2002).
    Article CAS PubMed Google Scholar
  10. Gallicchio, L. et al. Single nucleotide polymorphisms in inflammation-related genes and mortality in a community-based cohort in Washington County, Maryland. Am. J. Epidemiol. 167, 807–813 (2008).
    Article PubMed Google Scholar
  11. Wolpin, B.M. et al. Circulating insulin-like growth factor binding protein-1 and the risk of pancreatic cancer. Cancer Res. 67, 7923–7928 (2007).
    Article CAS PubMed Google Scholar
  12. Zeleniuch-Jacquotte, A. et al. Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: results of a prospective study. Int. J. Cancer 114, 323–327 (2005).
    Article CAS PubMed Google Scholar
  13. Hayes, R.B. et al. Methods for etiologic and early marker investigations in the PLCO trial. Mutat. Res. 592, 147–154 (2005).
    Article CAS PubMed Google Scholar
  14. Xu, W.H. et al. Joint effect of cigarette smoking and alcohol consumption on mortality. Prev. Med. 45, 313–319 (2007).
    Article PubMed PubMed Central Google Scholar
  15. Zheng, W. et al. The Shanghai Women's Health Study: rationale, study design, and baseline characteristics. Am. J. Epidemiol. 162, 1123–1131 (2005).
    Article PubMed Google Scholar
  16. Anderson, G.L. et al. Implementation of the Women's Health Initiative study design. Ann. Epidemiol. 13, S5–S17 (2003).
    Article PubMed Google Scholar
  17. Rexrode, K.M., Lee, I.M., Cook, N.R., Hennekens, C.H. & Buring, J.E. Baseline characteristics of participants in the Women's Health Study. J. Womens Health Gend. Based Med. 9, 19–27 (2000).
    Article CAS PubMed Google Scholar
  18. McWilliams, R.R. et al. Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. Cancer Res. 68, 4928–4935 (2008).
    Article CAS PubMed PubMed Central Google Scholar
  19. Eppel, A., Cotterchio, M. & Gallinger, S. Allergies are associated with reduced pancreas cancer risk: A population-based case-control study in Ontario, Canada. Int. J. Cancer 121, 2241–2245 (2007).
    Article CAS PubMed Google Scholar
  20. Duell, E.J. et al. Detecting pathway-based gene-gene and gene-environment interactions in pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 17, 1470–1479 (2008).
    Article CAS PubMed PubMed Central Google Scholar
  21. Hassan, M.M. et al. Risk factors for pancreatic cancer: case-control study. Am. J. Gastroenterol. 102, 2696–2707 (2007).
    Article PubMed PubMed Central Google Scholar
  22. Olson, S.H. et al. Allergies, variants in IL-4 and IL-4R alpha genes, and risk of pancreatic cancer. Cancer Detect. Prev. 31, 345–351 (2007).
    Article CAS PubMed Google Scholar
  23. Risch, H.A. Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. J. Natl. Cancer Inst. 95, 948–960 (2003).
    Article CAS PubMed Google Scholar
  24. Skol, A.D., Scott, L.J., Abecasis, G.R. & Boehnke, M. Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat. Genet. 38, 209–213 (2006).
    Article CAS PubMed Google Scholar
  25. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).
  26. Aird, I., Bentall, H.H. & Roberts, J.A. A relationship between cancer of stomach and the ABO blood groups. BMJ 1, 799–801 (1953).
    Article CAS PubMed PubMed Central Google Scholar
  27. Marcus, D.M. The ABO and Lewis blood-group system. Immunochemistry, genetics and relation to human disease. N. Engl. J. Med. 280, 994–1006 (1969).
    Article CAS PubMed Google Scholar
  28. Melzer, D. et al. A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet. 4, e1000072 (2008).
    Article PubMed PubMed Central Google Scholar
  29. Paré, G. et al. Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women. PLoS Genet. 4, e1000118 (2008).
    Article PubMed PubMed Central Google Scholar
  30. Yuan, X. et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am. J. Hum. Genet. 83, 520–528 (2008).
    Article CAS PubMed PubMed Central Google Scholar
  31. Itzkowitz, S.H. et al. Cancer-associated alterations of blood group antigen expression in the human pancreas. J. Natl. Cancer Inst. 79, 425–434 (1987).
    CAS PubMed Google Scholar
  32. Berman, D.M. et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425, 846–851 (2003).
    Article CAS PubMed Google Scholar
  33. Wolpin, B.M. et al. ABO blood group and the risk of pancreatic cancer. J. Natl. Cancer Inst. 101, 424–431 (2009).
    Article CAS PubMed PubMed Central Google Scholar
  34. Wigginton, J.E., Cutler, D.J. & Abecasis, G.R. A note on exact tests of Hardy-Weinberg equilibrium. Am. J. Hum. Genet. 76, 887–893 (2005).
    Article CAS PubMed PubMed Central Google Scholar
  35. Pritchard, J.K., Stephens, M. & Donnelly, P. Inference of population structure using multilocus genotype data. Genetics 155, 945–959 (2000).
    CAS PubMed PubMed Central Google Scholar
  36. Frazer, K.A. et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007).
    Article CAS PubMed Google Scholar
  37. Thomas, G. et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat. Genet. 40, 310–315 (2008).
    Article CAS PubMed Google Scholar
  38. Hunter, D.J. et al. A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat. Genet. 39, 870–874 (2007).
    Article CAS PubMed PubMed Central Google Scholar
  39. Yu, K. et al. Population substructure and control selection in genome-wide association studies. PLoS One 3, e2551 (2008).
    Article PubMed PubMed Central Google Scholar
  40. Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).
    Article CAS PubMed Google Scholar
  41. Patterson, N., Price, A.L. & Reich, D. Population structure and eigenanalysis. PLoS Genet. 2, e190 (2006).
    Article PubMed PubMed Central Google Scholar
  42. Sun, L., Wilder, K. & McPeek, M.S. Enhanced pedigree error detection. Hum. Hered. 54, 99–110 (2002).
    Article PubMed Google Scholar
  43. Lettre, G., Lange, C. & Hirschhorn, J.N. Genetic model testing and statistical power in population-based association studies of quantitative traits. Genet. Epidemiol. 31, 358–362 (2007).
    Article PubMed Google Scholar
  44. Higgins, J.P. & Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 21, 1539–1558 (2002).
    Article PubMed Google Scholar

Download references

Acknowledgements

The authors gratefully acknowledge the energy and contribution of our late colleague, Robert Welch. Additional acknowledgments are found in the Supplementary Note.

Author information

Author notes

  1. Laufey Amundadottir, Peter Kraft, Rachael Z Stolzenberg-Solomon, Charles S Fuchs, Stephen J Chanock, Patricia Hartge and Robert N Hoover: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, Laboratory of Translational Genomics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Laufey Amundadottir & Stephen J Chanock
  2. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Laufey Amundadottir, Rachael Z Stolzenberg-Solomon, Demetrius Albanes, Amy Hutchinson, Kevin B Jacobs, Julie B Mendelsohn, Gilles Thomas, Geoffrey S Tobias, Kai Yu, Stephen J Chanock, Patricia Hartge & Robert N Hoover
  3. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    Peter Kraft, Edward L Giovannucci, Susan E Hankinson, David J Hunter, Dominique S Michaud & Dimitrios Trichopoulos
  4. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
    Peter Kraft
  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
    Charles S Fuchs & Brian M Wolpin
  6. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Charles S Fuchs, Edward L Giovannucci, Susan E Hankinson, David J Hunter & Brian M Wolpin
  7. Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Gloria M Petersen, William Bamlet & Mariza de Andrade
  8. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA
    Alan A Arslan
  9. Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA
    Alan A Arslan & Anne Zeleniuch-Jacquotte
  10. New York University Cancer Institute, New York, New York, USA
    Alan A Arslan & Anne Zeleniuch-Jacquotte
  11. and Department of Gastroenterology and Hepatology, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, University Medical Center Utrecht, Utrecht, The Netherlands
    H Bas Bueno-de-Mesquita
  12. Department of Laboratory Medicine/Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
    Myron Gross
  13. Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA
    Kathy Helzlsouer
  14. Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia, USA
    Eric J Jacobs & Alpa V Patel
  15. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Andrea LaCroix, Charles Kooperberg & Margaret Mandelson
  16. Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA
    Wei Zheng & Xiao-Ou Shu
  17. Division of Cancer Prevention, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Christine D Berg
  18. Etiological Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
    Franco Berrino
  19. MRC Dunn Human Nutrition Unit, University of Cambridge, Cambridge, UK
    Sheila Bingham
  20. Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Julie E Buring
  21. Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, Massachusetts, USA
    Julie E Buring
  22. Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USA
    Paige M Bracci & Elizabeth A Holly
  23. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
    Federico Canzian & Rudolf Kaaks
  24. Institut National de la Santé et de la Recherche Médicale (INSERM) and Institut Gustave Roussy, Villejuif, France
    Françoise Clavel-Chapelon
  25. The Johns Hopkins Bloomberg School of Public Health, George W. Comstock Center for Public Health Research and Prevention, Hagerstown, Maryland, USA
    Sandra Clipp
  26. Cancer Care Ontario and Dalla Lana School of Public Health, University of Toronto, Ontario, Canada
    Michelle Cotterchio
  27. International Agency for Research on Cancer, Lyon, France
    Eric J Duell & Mazda Jenab
  28. College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
    John W Fox Jr
  29. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
    Steven Gallinger
  30. Divisions of Aging, Department of Medicine, Physicians' Health Study, Cardiovascular Medicine and Preventive 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
    J Michael Gaziano
  31. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
    Edward L Giovannucci
  32. Departments of Oncology, Pathology and Medicine, The Sol Goldman Pancreatic Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Michael Goggins
  33. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Barcelona, Spain
    Carlos A González
  34. Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden
    Göran Hallmans
  35. Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
    Manal Hassan & Donghui Li
  36. Core Genotyping Facility, Advanced Technology Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA
    Amy Hutchinson & Kevin B Jacobs
  37. Division of Endocrinology, Department of Internal Medicine and Center for Clinical and Translational Science, Diabetes and Metabolism, Ohio State University, Columbus, Ohio, USA
    Rebecca Jackson
  38. Bioinformed, LLC, Gaithersburg, Maryland, USA
    Kevin B Jacobs
  39. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Alison P Klein
  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
    Alison P Klein
  41. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Robert C Kurtz
  42. Division of Cancer Control and Population Sciences, Department of Health and Human Services, Epidemiology and Genetics Research Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Shannon M Lynch
  43. Group Health Center for Health Studies, Seattle, Washington, USA
    Margaret Mandelson
  44. Department of Oncology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Robert R McWilliams
  45. Division of Epidemiology, Public Health and Primary Care, Imperial College London, London, UK
    Dominique S Michaud, Petra H M Peeters & Elio Riboli
  46. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Sara H Olson
  47. Department of Cardiology and Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
    Kim Overvad
  48. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
    Petra H M Peeters
  49. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA
    Aleksandar Rajkovic
  50. Yale University School of Public Health, New Haven, Connecticut, USA
    Harvey A Risch & Herbert Yu
  51. Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
    Dimitrios Trichopoulos
  52. Division of Research, Kaiser Permanente, Northern California Region, Oakland, California, USA
    Stephen K Van Den Eeden
  53. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
    Jarmo Virtamo
  54. Department of Social and Preventive Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA
    Jean Wactawski-Wende

Authors

  1. Laufey Amundadottir
  2. Peter Kraft
  3. Rachael Z Stolzenberg-Solomon
  4. Charles S Fuchs
  5. Gloria M Petersen
  6. Alan A Arslan
  7. H Bas Bueno-de-Mesquita
  8. Myron Gross
  9. Kathy Helzlsouer
  10. Eric J Jacobs
  11. Andrea LaCroix
  12. Wei Zheng
  13. Demetrius Albanes
  14. William Bamlet
  15. Christine D Berg
  16. Franco Berrino
  17. Sheila Bingham
  18. Julie E Buring
  19. Paige M Bracci
  20. Federico Canzian
  21. Françoise Clavel-Chapelon
  22. Sandra Clipp
  23. Michelle Cotterchio
  24. Mariza de Andrade
  25. Eric J Duell
  26. John W Fox Jr
  27. Steven Gallinger
  28. J Michael Gaziano
  29. Edward L Giovannucci
  30. Michael Goggins
  31. Carlos A González
  32. Göran Hallmans
  33. Susan E Hankinson
  34. Manal Hassan
  35. Elizabeth A Holly
  36. David J Hunter
  37. Amy Hutchinson
  38. Rebecca Jackson
  39. Kevin B Jacobs
  40. Mazda Jenab
  41. Rudolf Kaaks
  42. Alison P Klein
  43. Charles Kooperberg
  44. Robert C Kurtz
  45. Donghui Li
  46. Shannon M Lynch
  47. Margaret Mandelson
  48. Robert R McWilliams
  49. Julie B Mendelsohn
  50. Dominique S Michaud
  51. Sara H Olson
  52. Kim Overvad
  53. Alpa V Patel
  54. Petra H M Peeters
  55. Aleksandar Rajkovic
  56. Elio Riboli
  57. Harvey A Risch
  58. Xiao-Ou Shu
  59. Gilles Thomas
  60. Geoffrey S Tobias
  61. Dimitrios Trichopoulos
  62. Stephen K Van Den Eeden
  63. Jarmo Virtamo
  64. Jean Wactawski-Wende
  65. Brian M Wolpin
  66. Herbert Yu
  67. Kai Yu
  68. Anne Zeleniuch-Jacquotte
  69. Stephen J Chanock
  70. Patricia Hartge
  71. Robert N Hoover

Contributions

L.A., P.K., R.Z.S.-S., C.S.F., G.M.P., K.B.J., S.M.L., J.B.M., G.S.T., S.J.C., P.H. and R.N.H. organized and designed the study. L.A., A.H., K.B.J., G.T. and S.J.C. supervised genotyping of samples. L.A., P.K., R.Z.S.-S., C.S.F., K.B.J., C.K., K.Y., S.J.C., P.H. and R.N.H. contributed to the design and execution of statistical analysis. LA., S.J.C., P.H. and R.N.H. wrote the first draft of the manuscript. R.Z.S.-S., C.S.F., G.M.P., A.A.A., H.B.B.-d.-M., M.G., K.H., E.J.J., A.L., W.Z., D.A., W.B., C.D.B., F.B., S.B., J.E.B., P.M.B., F.C., F.C.-C., S.C., M.C., M.d.A., E.J.D., J.W.F., S.G., J.M.G., E.L.G., M.G., C.A.G., G.H., S.E.H., M.H., E.A.H., D.J.H., R.J., M.J., R.K., A.P.K., C.K., R.C.K., D.L., M.M., R.R.M., D.S.M., S.H.O., K.O., A.V.P., P.H.M.P., A.R., E.R., H.A.R., X.-O.S., D.T., S.K.V.D.E., J.V., J.W.-W., B.M.W., H.Y. and A.Z.-J. conducted the epidemiologic studies and contributed samples to the PanScan GWAS and/or replication. All authors contributed to the writing of the manuscript.

Corresponding author

Correspondence toStephen J Chanock.

Supplementary information

Rights and permissions

About this article

Cite this article

Amundadottir, L., Kraft, P., Stolzenberg-Solomon, R. et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.Nat Genet 41, 986–990 (2009). https://doi.org/10.1038/ng.429

Download citation