Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer

• Published in: Nature genetics Vol. 40; no. 12; pp. 1426 - 1435
• Main Authors: Houlston, Richard S, Webb, Emily, Broderick, Peter, Pittman, Alan M, Di Bernardo, Maria Chiara, Lubbe, Steven, Chandler, Ian, Vijayakrishnan, Jayaram, Sullivan, Kate, Penegar, Steven, Carvajal-Carmona, Luis, Howarth, Kimberley, Jaeger, Emma, Spain, Sarah L, Walther, Axel, Barclay, Ella, Martin, Lynn, Gorman, Maggie, Domingo, Enric, Teixeira, Ana S, Kerr, David, Cazier, Jean-Baptiste, Niittymäki, Iina, Tuupanen, Sari, Karhu, Auli, Aaltonen, Lauri A, Tomlinson, Ian P M, Farrington, Susan M, Tenesa, Albert, Prendergast, James G D, Barnetson, Rebecca A, Cetnarskyj, Roseanne, Porteous, Mary E, Pharoah, Paul D P, 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, Dunlop, Malcolm G
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2008; Nature Publishing Group
• Subjects: Aged; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Disease susceptibility; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Function; Gene loci; Genetic aspects; Genetic Predisposition to Disease; Genetic variance; Genetic variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genome-Wide Association Study; Genomics; Human Genetics; Humans; Inflation; Male; Medical research; Medical sciences; Meta-analysis; Middle Aged; Quality control; Risk assessment; Risk factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; United Kingdom; Colonic disease; Rectal disease; Colorectal cancer; Digestive diseases; Intestinal disease; Identification; Malignant tumor; Locus; Cancer; Metaanalysis
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.262

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy. 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 × 10 −10 ), 16q22.1 (rs9929218, CDH1 ; P = 1.2 × 10 −8 ), 19q13.1 (rs10411210, RHPN2 ; P = 4.6 × 10 −9 ) and 20p12.3 (rs961253; P = 2.0 × 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.