A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3.

Journal article

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.

Authors: Tomlinson, I; Webb, E; Carvajal-Carmona, L; Broderick, P; Howarth, K

• Publication status: Published
• Journal: Nature genetics
• Volume: 40
• Issue: 5
• Pages: 623-630
• Publication date: 2008-05-01
• DOI: 10.1038/ng.111
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Adult; Genome, Human; Male; Aged; Genetic Linkage; Polymorphism, Single Nucleotide; EPICOLON Consortium; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 8; Alleles; Humans; Middle Aged; Colorectal Neoplasms; Genetic Predisposition to Disease; CORGI Consortium; Pedigree; Female; Eukaryotic Initiation Factor-3