A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
; Carvajal-Carmona, L; Broderick, P; Howarth, K; Pittman, AM; Spain, S; Lubbe, S; Walther, A; Sullivan, K; +67 more...Jaeger, E; Fielding, S; Rowan, A; Vijayakrishnan, J; Domingo, E; Chandler, I; Kemp, Z; Qureshi, M; Farrington, SM; Tenesa, A; Prendergast, JG; Barnetson, RA; Penegar, S; Barclay, E; Wood, W; Martin, L; Gorman, M; Thomas, H; Peto, J; Bishop, DT; Gray, R; Maher, ER; Lucassen, A; Kerr, D; Evans, DGR; CORGI Consortium; Schafmayer, C; Buch, S; Völzke, H; Hampe, J; Schreiber, S; John, U; Koessler, T; Pharoah, P; van Wezel, T; Morreau, H; Wijnen, JT; Hopper, JL; Southey, MC; Giles, GG; Severi, G; Castellví-Bel, S; Ruiz-Ponte, C; Carracedo, A; Castells, A; EPICOLON Consortium; Försti, A; Hemminki, K; Vodicka, P; Naccarati, A; Lipton, L; Ho, JW; Cheng, K; Sham, PC; Luk, J; Agúndez, JA; Ladero, JM; de la Hoya, M; Caldés, T; Niittymäki, I; Tuupanen, S; Karhu, A; Aaltonen, L; Cazier, J; Campbell, H; Dunlop, MG; Houlston, RS and
(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.