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

Brent W. Zanke, Celia M.T. Greenwood, Jagadish Rangrej, Rafal Kustra, Albert Tenesa, Susan M. Farrington, James Prendergast, Sylviane Olschwang, Theodore Chiang, Edgar Crowdy, Vincent Ferretti, Philippe Laflamme, Saravanan Sundararajan, Stéphanie Roumy, Jean François Olivier, Frédérick Robidoux, Robert Sladek, Alexandre Montpetit, Peter Campbell, Stephane BezieauAnne Marie O'Shea, George Zogopoulos, Michelle Cotterchio, Polly Newcomb, John McLaughlin, Ban Younghusband, Roger Green, Jane Green, Mary E.M. Porteous, Harry Campbell, Helene Blanche, Mourad Sahbatou, Emmanuel Tubacher, Catherine Bonaiti-Pellié, Bruno Buecher, Elio Riboli, Sebastien Kury, Stephen J. Chanock, John Potter, Gilles Thomas, Steven Gallinger, Thomas J. Hudson, Malcolm G. Dunlop

Research output: Contribution to journalArticle

Abstract

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 × 10-8) and 1.14 (trend; P = 1.32 × 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 × 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 × 10-11). This locus has also been implicated in prostate cancer.

Original languageEnglish (US)
Pages (from-to)989-994
Number of pages6
JournalNature genetics
Volume39
Issue number8
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Genetics

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    Zanke, B. W., Greenwood, C. M. T., Rangrej, J., Kustra, R., Tenesa, A., Farrington, S. M., Prendergast, J., Olschwang, S., Chiang, T., Crowdy, E., Ferretti, V., Laflamme, P., Sundararajan, S., Roumy, S., Olivier, J. F., Robidoux, F., Sladek, R., Montpetit, A., Campbell, P., ... Dunlop, M. G. (2007). Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nature genetics, 39(8), 989-994. https://doi.org/10.1038/ng2089