A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.
Tomlinson IP,
Webb E,
Carvajal-Carmona L,
Broderick P,
Howarth K,
Pittman AM,
Spain S,
Lubbe S,
Walther A,
Sullivan K,
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 DG;
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 KK,
Sham PC,
Luk J,
Agúndez JA,
Ladero JM,
de la Hoya M,
Caldés T,
Niittymäki I,
Tuupanen S,
Karhu A,
Aaltonen L,
Cazier JB,
Campbell H,
Dunlop MG,
Houlston RS.
Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK. ian.tomlinson@cancer.org.uk
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.
PMID: 18372905 [PubMed - indexed for MEDLINE]