Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

• Published in: Nature genetics Vol. 44; no. 7; pp. 770 - 776
• Main Authors: Dunlop, Malcolm G, Dobbins, Sara E, Farrington, Susan Mary, Jones, Angela M, Palles, Claire, Whiffin, Nicola, Tenesa, Albert, Spain, Sarah, Broderick, Peter, Ooi, Li-Yin, Domingo, Enric, Smillie, Claire, Henrion, Marc, Frampton, Matthew, Martin, Lynn, Grimes, Graeme, Gorman, Maggie, Semple, Colin, Ma, Yusanne P, Barclay, Ella, Prendergast, James, Cazier, Jean-Baptiste, Olver, Bianca, Penegar, Steven, Lubbe, Steven, Chander, Ian, Carvajal-Carmona, Luis G, Ballereau, Stephane, Lloyd, Amy, Vijayakrishnan, Jayaram, Zgaga, Lina, Rudan, Igor, Theodoratou, Evropi, Starr, John M, Deary, Ian, Kirac, Iva, Kovacević, Dujo, Aaltonen, Lauri A, Renkonen-Sinisalo, Laura, Mecklin, Jukka-Pekka, Matsuda, Koichi, Nakamura, Yusuke, Okada, Yukinori, Gallinger, Steven, Duggan, David J, Conti, David, Newcomb, Polly, Hopper, John, Jenkins, Mark A, Schumacher, Fredrick, Casey, Graham, Easton, Douglas, Shah, Mitul, Pharoah, Paul, Lindblom, Annika, Liu, Tao, Smith, Christopher G, West, Hannah, Cheadle, Jeremy P, Midgley, Rachel, Kerr, David J, Campbell, Harry, Tomlinson, Ian P, Houlston, Richard S
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2012; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/69; 631/208/727/2000; 692/699/67/1504/1885; Agriculture; Animal Genetics and Genomics; Arrays; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Case-Control Studies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Confidence intervals; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-dependent kinases; Deoxyribonucleic acid; DNA; DNA Polymerase III - genetics; DNA repair; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Function; Gene mutations; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study - methods; Genomes; Health aspects; Health risks; Human Genetics; Humans; letter; MEDICAL AND HEALTH SCIENCES; Medical sciences; MEDICIN OCH HÄLSOVETENSKAP; Membrane Proteins - genetics; Meta-analysis; Recruitment; Risk factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Studies; Tumors; United Kingdom; United Kingdom > UK; Colonic disease; Rectal disease; Colorectal cancer; Digestive diseases; Intestinal disease; Risk; Malignant tumor; Cancer
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2293

Richard Houlston and colleagues report a genome-wide association study for colorectal cancer. They report three loci newly associated with colorectal cancer, bringing the total number of common susceptibility loci to 20.
We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near
CDKN1A
;
P
= 1.14 × 10
−10
), 11q13.4 (rs3824999, intronic to
POLD3
;
P
= 3.65 × 10
−10
) and Xp22.2 (rs5934683, near
SHROOM2
;
P
= 7.30 × 10
−10
) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.