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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-07-08

AUTHORS

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

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 × 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. More... »

PAGES

984-988

Journal

TITLE

Nature Genetics

ISSUE

8

VOLUME

39

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng2085

DOI

http://dx.doi.org/10.1038/ng2085

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048660016

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17618284


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