A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
; Carvajal-Carmona, Luis; Broderick, Peter; Howarth, Kimberley; Pittman, Alan M; Spain, Sarah; Lubbe, Steven; Walther, Axel; Sullivan, Kate; +67 more...Jaeger, Emma; Fielding, Sarah; Rowan, Andrew; Vijayakrishnan, Jayaram; Domingo, Enric; Chandler, Ian; Kemp, Zoe; Qureshi, Mobshra; Farrington, Susan M; Tenesa, Albert; Prendergast, James GD; Barnetson, Rebecca A; Penegar, Steven; Barclay, Ella; Wood, Wendy; Martin, Lynn; Gorman, Maggie; Thomas, Huw; Peto, Julian; Bishop, D Timothy; Gray, Richard; Maher, Eamonn R; Lucassen, Anneke; Kerr, David; Evans, D Gareth R; CORGI Consortium; Schafmayer, Clemens; Buch, Stephan; Völzke, Henry; Hampe, Jochen; Schreiber, Stefan; John, Ulrich; Koessler, Thibaud; Pharoah, Paul; van Wezel, Tom; Morreau, Hans; Wijnen, Juul T; Hopper, John L; Southey, Melissa C; Giles, Graham G; Severi, Gianluca; Castellví-Bel, Sergi; Ruiz-Ponte, Clara; Carracedo, Angel; Castells, Antoni; EPICOLON Consortium; Försti, Asta; Hemminki, Kari; Vodicka, Pavel; Naccarati, Alessio; Lipton, Lara; Ho, Judy WC; Cheng, KK; Sham, Pak C; Luk, J; Agúndez, Jose AG; Ladero, Jose M; de la Hoya, Miguel; Caldés, Trinidad; Niittymäki, Iina; Tuupanen, Sari; Karhu, Auli; Aaltonen, Lauri; Cazier, Jean-Baptiste; Campbell, Harry; Dunlop, Malcolm G; and Houlston, Richard S
(2008)
A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
Nature genetics, 40 (5).
pp. 623-630.
ISSN 1061-4036
DOI: 10.1038/ng.111
To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.