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Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

2010; Nature Portfolio; Volume: 42; Issue: 11 Linguagem: Inglês

10.1038/ng.670

1546-1718

Richard S. Houlston, Jeremy P. Cheadle, Sara E. Dobbins, Albert Tenesa, Angela M. Jones, Kimberley Howarth, Sarah L. Spain, Peter Broderick, Enric Domingo, Susan M. Farrington, James Prendergast, Alan Pittman, Evropi Τheodoratou, Christopher G. Smith, Bianca Olver, Axel Walther, Rebecca A. Barnetson, Michael Churchman, Emma Jaeger, Steven Penegar, Ella Barclay, Lynn Martin, Maggie Gorman, R. Mager, Elaine Johnstone, Rachel Midgley, Iina Niittymäki, Sari Tuupanen, James Colley, Shelley Idziaszczyk, Huw Thomas, Anneke Lucassen, D. Gareth Evans, Eamonn R. Maher, Tim Maughan, Antigone S. Dimas, Emmanouil T. Dermitzakis, Jean‐Baptiste Cazier, Lauri A. Aaltonen, Paul D.P. Pharoah, Rachel Kerr, Luis G. Carvajal‐Carmona, Harry Campbell, Malcolm G. Dunlop, Ian Tomlinson,

Cancer-related molecular mechanisms research

Ian Tomlinson, Richard Houlston, Malcolm Dunlop and colleagues report results of a large genome-wide association study of colorectal cancer. They identify four new risk loci and suggest that many more loci of similar effect size are likely to exist. Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10−10 and rs6687758, OR = 1.09, P = 2.27 × 10−9), 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10−8), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10−10 and rs7136702, OR = 1.06, P = 4.02 × 10−8) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10−10). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.