A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3 |
| |
| Authors: | Tomlinson Ian P M,Webb Emily,Carvajal-Carmona Luis,Broderick Peter,Howarth Kimberley,Pittman Alan M,Spain Sarah,Lubbe Steven,Walther Axel,Sullivan Kate,Jaeger Emma,Fielding Sarah,Rowan Andrew,Vijayakrishnan Jayaram,Domingo Enric,Chandler Ian,Kemp Zoe,Qureshi Mobshra,Farrington Susan M,Tenesa Albert,Prendergast James G D,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 |
| |
| Affiliation: | Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, UK. ian.tomlinson@cancer.org.uk |
| |
| Abstract: | 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. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
