A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21
Abstract
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 x 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 x 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 x 10(-5)). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.
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Recent genome-wide association studies have detected SNPs significantly associated with breast cancer, colorectal cancer, type 2 diabetes, and heart disease, among other diseases.
“This idea, combined with the development of efficient methods for surveying large numbers of SNPs, has led to the many recent genome-wide association (GWA) studies that have detected SNPs that are significantly associated with breast cancer79,80, colorectal cancer81,82, type 2 diabetes83–86 and heart disease87,88, among other diseases.”
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- Authors
- the CORGI Consortium, Tomlinson, I., Webb, E., Carvajal-Carmona, L., Broderick, P., Kemp, Z., Spain, S., Penegar, S., Chandler, I., Gorman, M., Wood, W., Barclay, E., Lubbe, S., Martin, L., Sellick, G., Jaeger, E., Hubner, R., Wild, R., Rowan, A., Fielding, S., Howarth, K., Silver, A., Atkin, W., Muir, K., Logan, R., Kerr, D., Johnstone, E., Sieber, O., Gray, R., Thomas, H., Peto, J., Cazier, J.-B., & Houlston, R.
- Affiliations
- Cancer Research UK (GB)
- Institute of Cancer Research (GB)
- Queen Mary University of London (GB)
- University of Nottingham (GB)
- University of Oxford (GB)
- University of Birmingham (GB)
- Corresponding author
- Tomlinson, Ian
- Houlston, Richard
- ORCID
- Tomlinson, Ian
- Webb, Emily
- Broderick, Peter
- Kemp, Zoe
- Spain, Sarah
- Penegar, Steven
- Lubbe, Steven
- Martin, Lynn
- Hubner, Richard
- Rowan, Andrew
- Fielding, Sarah
- Howarth, Kimberley
- Silver, Andrew
- Atkin, Wendy
- Muir, Kenneth
- Logan, Richard
- Kerr, David
- Johnstone, Elaine
- Sieber, Oliver
- Gray, Richard
- Thomas, Huw
- Peto, Julian
- Cazier, Jean-Baptiste
- Houlston, Richard
- Venue
- Nature Genetics
- Published
- 2007-07-08
- Volume
- 39
- Issue
- 8
- Pages
- 984-988
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1991460649
- Cited by
- 808
- References
- 2
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 17 · 2022: 15 · 2021: 20 · 2020: 17 · 2019: 26 · 2018: 28 · 2017: 41 · 2016: 42 · 2015: 48 · 2014: 46 · 2013: 53 · 2012: 87
- FWCI
- 53.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Screening and Detection
- Keywords
- colorectal cancer, 8q24.21, rs6983267, tag SNPs, genetic susceptibility, colorectal adenoma, low-penetrance alleles, cancer susceptibility
- MeSH terms
- Aged, Chromosomes, Human, Pair 8, Female, Genotype, Humans, Male, Middle Aged, Colorectal Neoplasms, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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