Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.
; Broderick, Peter; Pittman, Alan M; Di Bernardo, Maria Chiara; Lubbe, Steven; Chandler, Ian; Vijayakrishnan, Jayaram; Sullivan, Kate; +43 more...Penegar, Steven; Colorectal Cancer Association Study Consortium; Carvajal-Carmona, Luis; Howarth, Kimberley; Jaeger, Emma; Spain, Sarah L; Walther, Axel; Barclay, Ella; Martin, Lynn; Gorman, Maggie; Domingo, Enric; Teixeira, Ana S; CoRGI Consortium; Kerr, David; Cazier, Jean-Baptiste; Niittymäki, Iina; Tuupanen, Sari; Karhu, Auli; Aaltonen, Lauri A; Tomlinson, Ian PM; Farrington, Susan M; Tenesa, Albert; Prendergast, James GD; Barnetson, Rebecca A; Cetnarskyj, Roseanne; Porteous, Mary E; Pharoah, Paul DP; Koessler, Thibaud; Hampe, Jochen; Buch, Stephan; Schafmayer, Clemens; Tepel, Jurgen; Schreiber, Stefan; Völzke, Henry; Chang-Claude, Jenny; Hoffmeister, Michael; Brenner, Hermann; Zanke, Brent W; Montpetit, Alexandre; Hudson, Thomas J; Gallinger, Steven; Campbell, Harry; and Dunlop, Malcolm G
(2008)
Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.
Nature genetics, 40 (12).
pp. 1426-1435.
ISSN 1061-4036
DOI: 10.1038/ng.262
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.