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Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. 2007
Brent W Zanke, and
Celia M T Greenwood, and
Jagadish Rangrej, and
Rafal Kustra, and
Albert Tenesa, and
Susan M Farrington, and
James Prendergast, and
Sylviane Olschwang, and
Theodore Chiang, and
Edgar Crowdy, and
Vincent Ferretti, and
Philippe Laflamme, and
Saravanan Sundararajan, and
Stéphanie Roumy, and
Jean-François Olivier, and
Frédérick Robidoux, and
Robert Sladek, and
Alexandre Montpetit, and
Peter Campbell, and
Stephane Bezieau, and
Anne Marie O'Shea, and
George Zogopoulos, and
Michelle Cotterchio, and
Polly Newcomb, and
John McLaughlin, and
Ban Younghusband, and
Roger Green, and
Jane Green, and
Mary E M Porteous, and
Harry Campbell, and
Helene Blanche, and
Mourad Sahbatou, and
Emmanuel Tubacher, and
Catherine Bonaiti-Pellié, and
Bruno Buecher, and
Elio Riboli, and
Sebastien Kury, and
Stephen J Chanock, and
John Potter, and
Gilles Thomas, and
Steven Gallinger, and
Thomas J Hudson, and
Malcolm G Dunlop
Cancer Care Ontario, 620 University Avenue, Toronto, Ontario M5G 1L7, Canada.
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 x 10(-8)) and 1.14 (trend; P = 1.32 x 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 x 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 x 10(-11)). This locus has also been implicated in prostate cancer.
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