Journal Article

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

Lubbe, Steven, Barnetson, Rebecca A, Gray, Richard, Ho, Judy WC, Peto, Julian, Spain, Sarah, Schreiber, Stefan, Qureshi, Mobshra, Barclay, Ella, Southey, Melissa C, Buch, Stephan, Cheng, K K, Tenesa, Albert, Koessler, Thibaud, Sham, Pak C, Gorman, Maggie, Dunlop, Malcolm G, Hampe, Jochen, Hopper, John L, Cazier, Jean-Baptiste, Caldés, Trinidad, Jaeger, Emma, Wood, Wendy, Howarth, Kimberley, Penegar, Steven, Försti, Asta, Tomlinson, Ian PM, Thomas, Huw, Pittman, Alan M, Vijayakrishnan, Jayaram, Kerr, David, de la Hoya, Miguel, Karhu, Auli, Kemp, Zoe, Chandler, Ian, Aaltonen, Lauri, Schafmayer, Clemens, Carvajal-Carmona, Luis, Castells, Antoni, Lipton, Lara, Rowan, Andrew, Völzke, Henry, Hemminki, Kari, Campbell, Harry, Houlston, Richard S, Webb, Emily, Agúndez, Jose AG, Tuupanen, Sari, Castellví-Bel, Sergi, Fielding, Sarah, Prendergast, James GD, John, Ulrich, Ruiz-Ponte, Clara, Farrington, Susan M, Vodicka, Pavel, Evans, D Gareth R, van Wezel, Tom, Severi, Gianluca, Luk, J, Carracedo, Angel, Morreau, Hans, Naccarati, Alessio, Sullivan, Kate, Walther, Axel, Martin, Lynn, Giles, Graham G, Bishop, D Timothy, Lucassen, A

2008

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Adult / Aged / Agriculture / Alleles / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosomes / Chromosomes, Human, Pair 10 - genetics / Chromosomes, Human, Pair 8 - genetics / Classical genetics, quantitative genetics, hybrids / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - genetics / Eukaryotic Initiation Factor-3 - genetics / Female / Fundamental and applied biological sciences. Psychology / Gastroenterology. Liver. Pancreas. Abdomen / Gene Function / Gene loci / Genetic Linkage / Genetic Predisposition to Disease / Genetic research / Genetic testing / Genetics of eukaryotes. Biological and molecular evolution / Genome, Human / Histology / Human Genetics / Humans / letter / Male / Medical sciences / Methods, theories and miscellaneous / Middle Aged / Pedigree / Polymorphism, Single Nucleotide / Quality control / Regression analysis / Stomach. Duodenum. Small intestine. Colon. Rectum. Anus / Tumors