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

Reference details

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, Schafmayer C, Buch S, Volzke 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, Castellvi-Bel S, Ruiz-Ponte C, Carracedo A, Castells A, Forsti A, Hemminki K, Vodicka P, Naccarati A, Lipton L, Ho JW, Cheng KK, Sham PC, Luk J, Agundez JA, Ladero JM, de la Hoya M, Caldes T, Niittymaki I, Tuupanen S, Karhu A, Aaltonen L, Cazier JB, Campbell H, Dunlop MG, Houlston RS (2008) A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet 40:623-630

ABTRACT

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="">

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