Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer.
COGENT Study None., Houlston RS., Webb E., Broderick P., Pittman AM., Di Bernardo MC., Lubbe S., Chandler I., Vijayakrishnan J., Sullivan K., Penegar S., Colorectal Cancer Association Study Consortium None., Carvajal-Carmona L., Howarth K., Jaeger E., Spain SL., Walther A., Barclay E., Martin L., Gorman M., Domingo E., Teixeira AS., CoRGI Consortium None., Kerr D., Cazier J-B., Niittymäki I., Tuupanen S., Karhu A., Aaltonen LA., Tomlinson IPM., Farrington SM., Tenesa A., Prendergast JGD., Barnetson RA., Cetnarskyj R., Porteous ME., Pharoah PDP., Koessler T., Hampe J., Buch S., Schafmayer C., Tepel J., Schreiber S., Völzke H., Chang-Claude J., Hoffmeister M., Brenner H., Zanke BW., Montpetit A., Hudson TJ., Gallinger S., Campbell H., Dunlop MG.
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.