A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21.
Nat Genet
; 39(8): 984-8, 2007 Aug.
Article
in En
| MEDLINE
| ID: mdl-17618284
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Genetic Predisposition to Disease
/
Polymorphism, Single Nucleotide
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Nat Genet
Journal subject:
GENETICA MEDICA
Year:
2007
Document type:
Article
Affiliation country:
United kingdom