Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24
Abstract
Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.
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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.”
From Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. (2008) · cites this paper as [82]
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- Authors
- Zanke, B. W., Greenwood, C. M., Rangrej, J., Kustra, R., Tenesa, A., Farrington, S. M., Prendergast, J., Olschwang, S., Chiang, T., Crowdy, E., Ferretti, V., Laflamme, P., Sundararajan, S., Roumy, S., Olivier, J.-F., Robidoux, F., Sladek, R., Montpetit, A., Campbell, P., Bezieau, S., O'Shea, A. M., Zogopoulos, G., Cotterchio, M., Newcomb, P., McLaughlin, J., Younghusband, B., Green, R., Green, J., Porteous, M. E. M., Campbell, H., Blanche, H., Sahbatou, M., Tubacher, E., Bonaiti-Pellié, C., Buecher, B., Riboli, E., Kury, S., Chanock, S. J., Potter, J., Thomas, G., Gallinger, S., Hudson, T. J., & Dunlop, M. G.
- Affiliations
- Cancer Care Ontario (CA)
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Western General Hospital (GB)
- Inserm (FR)
- McGill University and Génome Québec Innovation Centre (CA)
- Mount Sinai Hospital (CA)
- Fred Hutch Cancer Center (US)
- Memorial University of Newfoundland (CA)
- University of Edinburgh (GB)
- Fondation Jean Dausset-CEPH (FR)
- Centre Hospitalier Universitaire de Nantes (FR)
- United States Department of Health and Human Services (US)
- National Cancer Institute (US)
- Ontario Institute for Cancer Research (CA)
- Corresponding author
- Hudson, Thomas J
- ORCID
- Greenwood, Celia MT
- Kustra, Rafal
- Tenesa, Albert
- Farrington, Susan M
- Prendergast, James
- Olschwang, Sylviane
- Ferretti, Vincent
- Sladek, Robert
- Campbell, Peter
- Zogopoulos, George
- Cotterchio, Michelle
- Newcomb, Polly
- McLaughlin, John
- Green, Jane
- Buecher, Bruno
- Chanock, Stephen J
- Potter, John
- Thomas, Gilles
- Hudson, Thomas J
- Dunlop, Malcolm G
- Venue
- Nature Genetics
- Published
- 2007-07-08
- Volume
- 39
- Issue
- 8
- Pages
- 989-994
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2168272873
- Cited by
- 724
- References
- 2
- Citations by year
- 2025: 5 · 2024: 7 · 2023: 22 · 2022: 13 · 2021: 17 · 2020: 11 · 2019: 20 · 2018: 26 · 2017: 28 · 2016: 33 · 2015: 46 · 2014: 47 · 2013: 45 · 2012: 69
- FWCI
- 51.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (RFA # CA-95-011, U01CA074794, U01CA074783, U01 CA076783)
- 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, cancer susceptibility, chromosome 8q24, single nucleotide polymorphisms, genetic association, prostate cancer, cancer risk loci
- MeSH terms
- Chromosome Mapping, Chromosomes, Human, Pair 8, Humans, Middle Aged, Colorectal Neoplasms, Linkage Disequilibrium, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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