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

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 × 10−13 overall; P = 6.9 × 10−12 replication), and rs16892766, at 8q23.3 (P = 3.3 × 10−18 overall; P = 9.6 × 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.

DOI: 10.1038/ng.111

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@article{Tomlinson2008AGA, title={A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3}, author={Ian Tomlinson and Emily L. Webb and Luis G Carvajal-Carmona and Peter Broderick and Kimberley M. Howarth and Alan M. Pittman and Sarah L Spain and Steven J. Lubbe and Axel Walther and Kate Sullivan and Emma E. M. Jaeger and Sarah Fielding and Andrew Rowan and Jayaram Vijayakrishnan and Enric Domingo and Ian P Chandler and Zoe E Kemp and Mobshra Qureshi and Susan Mary Farrington and A. Tenesa and James G D Prendergast and Rebecca A Barnetson and Steven Penegar and Ella Barclay and Wendy Wood and Lynn Martin and Maggie Gorman and Huw JM Thomas and Julian Peto and D Timothy Bishop and Richard Gray and Eamonn R. Maher and Anneke M Lucassen and D. Kerr and D Gareth R Evans and Clemens Schafmayer and Stephan Buch and Henry V{\"{o}lzke and Jochen Hampe and Stefan Schreiber and Ulrich John and Thibaud Koessler and Paul D. P. Pharoah and Tom van Wezel and Hans Morreau and Juul Th Wijnen and John L. Hopper and Melissa C. Southey and Graham G. Giles and Gianluca Severi and Sergi Castellv{\'i}-Bel and Clara Ru{\'i}z-Ponte and {\'A}ngel Carracedo and Antoni Castells and Asta Foersti and Kari Hemminki and Pavel Erik Vodicka and Alessio Naccarati and Lara R. Lipton and Judy Wai-chu Ho and Kar-keung Cheng and Pak C. Sham and J. Luk and Jos{\'e} A G Ag{\'u}ndez and Jos{\'e} Mar{\'i}a Ladero and Miguel de la Hoya and Trinidad Cald{\'e}s and Iina Niittym{\"a}ki and Sari Tuupanen and Auli Karhu and Lauri A. Aaltonen and Jean-Baptiste Cazier and Harry Campbell and Malcolm G. Dunlop and Richard S. Houlston}, journal={Nature Genetics}, year={2008}, volume={40}, pages={623-630} }