title: 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.
authors.affiliation: Molecular and Population Genetics Laboratory, Cancer Research UK, London WC2A 3PX, UK. ian.tomlinson@cancer.org.uk
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Emily
authors.initials: E
authors.lastname: Webb
authors.forename: Luis
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authors.lastname: Carvajal-Carmona
authors.forename: Peter
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authors.lastname: Broderick
authors.forename: Zoe
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authors.lastname: Kemp
authors.forename: Sarah
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authors.lastname: Spain
authors.forename: Steven
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authors.lastname: Penegar
authors.forename: Ian
authors.initials: I
authors.lastname: Chandler
authors.forename: Maggie
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authors.lastname: Gorman
authors.forename: Wendy
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authors.lastname: Wood
authors.forename: Ella
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authors.lastname: Barclay
authors.forename: Steven
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authors.lastname: Lubbe
authors.forename: Lynn
authors.initials: L
authors.lastname: Martin
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Sellick
authors.forename: Emma
authors.initials: E
authors.lastname: Jaeger
authors.forename: Richard
authors.initials: R
authors.lastname: Hubner
authors.forename: Ruth
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authors.lastname: Wild
authors.forename: Andrew
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authors.lastname: Rowan
authors.forename: Sarah
authors.initials: S
authors.lastname: Fielding
authors.forename: Kimberley
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authors.lastname: Howarth
authors.forename: Andrew
authors.initials: A
authors.lastname: Silver
authors.forename: Wendy
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authors.lastname: Atkin
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.forename: Richard
authors.initials: R
authors.lastname: Logan
authors.forename: David
authors.initials: D
authors.lastname: Kerr
authors.forename: Elaine
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authors.lastname: Johnstone
authors.forename: Oliver
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authors.lastname: Sieber
authors.forename: Richard
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authors.lastname: Gray
authors.forename: Huw
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authors.lastname: Thomas
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Cazier
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
mesh_terms: D000368:Aged; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide