Letter abstract

Nature Genetics 39, 989 - 994 (2007)
Published online: 8 July 2007 | doi:10.1038/ng2089

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Brent W Zanke1,2,3, Celia MT Greenwood1,4,5, Jagadish Rangrej4, Rafal Kustra1,5, Albert Tenesa6, Susan M Farrington6, James Prendergast6, Sylviane Olschwang7, Theodore Chiang4, Edgar Crowdy4, Vincent Ferretti8, Philippe Laflamme8, Saravanan Sundararajan8, Stéphanie Roumy8, Jean-François Olivier8, Frédérick Robidoux8, Robert Sladek8, Alexandre Montpetit8, Peter Campbell9, Stephane Bezieau10, Anne Marie O'Shea9, George Zogopoulos9, Michelle Cotterchio1,5, Polly Newcomb11, John McLaughlin1,9, Ban Younghusband12, Roger Green12, Jane Green12, Mary E M Porteous13, Harry Campbell6,14, Helene Blanche15, Mourad Sahbatou15, Emmanuel Tubacher15, Catherine Bonaiti-Pellié16, Bruno Buecher10, Elio Riboli17, Sebastien Kury10, Stephen J Chanock18, John Potter11, Gilles Thomas19, Steven Gallinger1,9, Thomas J Hudson2,8 & Malcolm G Dunlop6

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Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2–4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1–4 of 1.18 (trend; P = 1.41 times 10-8) and 1.14 (trend; P = 1.32 times 10-5), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07–1.26; P = 5.05 times 10-4). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12–1.23; P = 3.16 times 10-11). This locus has also been implicated in prostate cancer1, 2, 3.

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  1. Cancer Care Ontario, 620 University Avenue, Toronto, Ontario M5G 1L7, Canada.
  2. The Ontario Institute for Cancer Research, 101 College St., Toronto M5G 2L7, Canada.
  3. The University of Ottawa, Faculty of Medicine, Division of Hematology, 501 Smythe Road, Ottawa K1H 8L6, Canada.
  4. Genetics and Genome Biology, Hospital for Sick Children, 15-703 TMDT East, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
  5. University of Toronto, Department of Public Health Sciences Health Sciences Building, 155 College Street, Toronto M5T 3M7, Canada.
  6. Colon Cancer Genetics Group, University of Edinburgh Cancer Research Centre and UK Medical Research Council (MRC) Human Genetics Unit, Western General Hospital, Edinburgh UK EH4 2XU, UK.
  7. INSERM U599, Institut Paoli Calmettes, F-13009 Marseille, France.
  8. The McGill University and Genome Quebec Innovation Centre, 700 Dr. Penfield Ave., Montreal, Quebec H3G 1A4, Canada.
  9. Samuel Lunenfeld Research Institute, Mount Sinai Hospital and University of Toronto, 600 University Ave., Toronto, Ontario M5G 1X5, Canada.
  10. EA3823 and Institut des Maladies de l'Appareil Digestif (IMAD), Centre Hospitalier Universitaire Hotel-Dieu, 44093 Nantes Cedex 01, France.
  11. Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA.
  12. Memorial University of Newfoundland, St. John's, Newfoundland A1C 5S7, Canada.
  13. Clinical Genetics Department, University of Edinburgh, Edinburgh EH4 2XU, UK.
  14. Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
  15. Centre d'Etude du Polymorphisme Humain,27 rue Juliette Dodu, F-75010 Paris, France.
  16. Institut National de la Santé et de la Recherche Médicale (INSERM) U535, Hopital Paul Brousse, BP1000, 94800 Villejuif, France.
  17. Faculty of Medicine, Imperial College W2 1PG, London, UK.
  18. Center for Cancer Research, National Cancer Institute (NCI), US National Institutes of Health (NIH), Department of Health and Human Services (DHHS), and Division of Cancer Genetics and Epidemiology, NCI, NIH, DHHS, 8717 Grovemont Circle, Gaithersburg, Maryland 20877, USA.
  19. Division of Cancer Epidemiology and Genetics National Cancer Institute 8717 Grovemont Circle, Bethesda, Maryland 20892-4605, USA.

Correspondence to: Thomas J Hudson2,8 e-mail: tom.hudson@oicr.on.ca

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