| Literature DB >> 18372905 |
Ian P M Tomlinson1, Emily Webb, Luis Carvajal-Carmona, Peter Broderick, Kimberley Howarth, Alan M Pittman, Sarah Spain, Steven Lubbe, Axel Walther, Kate Sullivan, Emma Jaeger, Sarah Fielding, Andrew Rowan, Jayaram Vijayakrishnan, Enric Domingo, Ian Chandler, Zoe Kemp, Mobshra Qureshi, Susan M Farrington, Albert Tenesa, James G D Prendergast, Rebecca A Barnetson, Steven Penegar, Ella Barclay, Wendy Wood, Lynn Martin, Maggie Gorman, Huw Thomas, Julian Peto, D Timothy Bishop, Richard Gray, Eamonn R Maher, Anneke Lucassen, David Kerr, D Gareth R Evans, Clemens Schafmayer, Stephan Buch, Henry Völzke, Jochen Hampe, Stefan Schreiber, Ulrich John, Thibaud Koessler, Paul Pharoah, Tom van Wezel, Hans Morreau, Juul T Wijnen, John L Hopper, Melissa C Southey, Graham G Giles, Gianluca Severi, Sergi Castellví-Bel, Clara Ruiz-Ponte, Angel Carracedo, Antoni Castells, Asta Försti, Kari Hemminki, Pavel Vodicka, Alessio Naccarati, Lara Lipton, Judy W C Ho, K K Cheng, Pak C Sham, J Luk, Jose A G Agúndez, Jose M Ladero, Miguel de la Hoya, Trinidad Caldés, Iina Niittymäki, Sari Tuupanen, Auli Karhu, Lauri Aaltonen, Jean-Baptiste Cazier, Harry Campbell, Malcolm G Dunlop, Richard S Houlston.
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.Entities:
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Year: 2008 PMID： 18372905 DOI： 10.1038/ng.111
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330