Journal Article

A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21

Wild, Ruth, Johnstone, Elaine, Carvajal-Carmona, Luis, Atkin, Wendy, Lubbe, Steven, Rowan, Andrew, Webb, Emily, Muir, Kenneth, Gray, Richard, Hubner, Richard, Houlston, Richard, Peto, Julian, Fielding, Sarah, Spain, Sarah, Barclay, Ella, Sieber, Oliver, Gorman, Maggie, Tomlinson, Ian, Cazier, Jean-Baptiste, Jaeger, Emma, Wood, Wendy, Penegar, Steven, Martin, Lynn, Howarth, Kimberley, Thomas, Huw, Kerr, David, Broderick, Peter, Sellick, Gabrielle, Silver, Andrew, Kemp, Zoe, Chandler, Ian, Logan, Richard

2007

Overview

Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 familial colorectal tumor cases and 960 controls. The most strongly associated SNP ( P = 1.72 × 10 −7 , allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 × 10 −14 (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16–1.39) and 1.47 (95% c.i.: 1.34–1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10–1.34; P = 6.89 × 10 −5 ). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Aged / Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosomes, Human, Pair 8 / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - genetics / Diagnosis / Female / Fundamental and applied biological sciences. Psychology / Gastroenterology. Liver. Pancreas. Abdomen / Gene Function / Genetic aspects / Genetic Predisposition to Disease / Genetics of eukaryotes. Biological and molecular evolution / Genomics / Genotype / Human Genetics / Humans / letter / Male / Medical sciences / Middle Aged / Physiological aspects / Polymorphism, Single Nucleotide / Population genetics / Risk factors / Single nucleotide polymorphisms / Stomach. Duodenum. Small intestine. Colon. Rectum. Anus / Tumors