Letter abstract
Nature Genetics 39, 984 - 988 (2007)
Published online: 8 July 2007 | doi:10.1038/ng2085
A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21
Ian Tomlinson1,2, Emily Webb3,13, Luis Carvajal-Carmona1,13, Peter Broderick3,13, Zoe Kemp1,13, Sarah Spain1,13, Steven Penegar3, Ian Chandler3, Maggie Gorman1, Wendy Wood3, Ella Barclay1, Steven Lubbe3, Lynn Martin1, Gabrielle Sellick3, Emma Jaeger1, Richard Hubner3, Ruth Wild3, Andrew Rowan1, Sarah Fielding3, Kimberley Howarth1, the CORGI Consortium, Andrew Silver2, Wendy Atkin4, Kenneth Muir5, Richard Logan5, David Kerr6, Elaine Johnstone6, Oliver Sieber7, Richard Gray8, Huw Thomas9, Julian Peto10,11, Jean-Baptiste Cazier12 & Richard Houlston3
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.
- Molecular and Population Genetics Laboratory, Cancer Research UK, London WC2A 3PX, UK.
- Institute of Cancer, Bart's and the London Medical School, Queen Mary College, University of London, UK.
- Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK.
- Colorectal Cancer Unit, Cancer Research UK, St Mark's Hospital, Harrow HA1 3UJ, UK.
- University of Nottingham, Division of Epidemiology and Public Health, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK.
- Department of Clinical Pharmacology, Oxford University, Radcliffe Infirmary, Oxford, OX2 6HA, UK.
- Cancer and Immunogenetics Laboratory, Weatherall Institute for Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
- Birmingham Clinical Trials Unit, University of Birmingham, Birmingham B15 2RR, UK.
- Family Cancer Clinic, Cancer Research UK, St Mark's Hospital, Harrow HA1 3UJ, UK.
- Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.
- Section of Epidemiology, Institute of Cancer Research, Surrey SM2 5NG, UK.
- Bioinformatics and Biostatistics, Cancer Research UK, London WC2A 3PX, UK.
- These authors contributed equally to this work.
Correspondence to: Richard Houlston3 e-mail: richard.houlston@icr.ac.uk
Correspondence to: Ian Tomlinson1,2 e-mail: ian.tomlinson@cancer.org.uk
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