Characterization of the association between 8q24 and colon cancer: gene-environment exploration and meta-analysis.
BACKGROUND
Genome-wide association studies and subsequent replication studies have shown that single nucleotide polymorphisms (SNPs) in the chromosomal region 8q24 are associated with colorectal cancer susceptibility.


METHODS
We examined 11 SNP markers in the 8q24 region between 128.47 and 128.54 Mb, using a total of 1,987 colon cases and 2,339 controls who self-reported as white from two independent, well-characterized study populations. Analysis was performed separately within each study, and combined using random effects meta-analysis. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) and to test for effect modification by known colon cancer risk factors. We also performed a meta-analysis combining our results with previous studies.


RESULTS
We observed evidence of association for four SNPs in low to high linkage disequilibrium (r2 ranging from 0.18 to 0.93) localized in a 16.2 kb region defined by rs10505477 and rs1056368. The combined results for our two studies of colon cancer showed an OR of 1.10 (95% CI: 1.01-1.20, Ptrend = 0.023), and a meta-analysis of our results with previously reported studies of colon and colorectal cancer strongly support the association for this SNP (combined OR for rs6983267 = 1.21, 95% CI: 1.18-1.24, p = 5.5 × 10-44). We did not observe any notable evidence of effect modification by known colon cancer risk factors, and risk did not differ significantly by tumor site or stage.


CONCLUSIONS
Our study confirms the association between polymorphisms on chromosome 8q24 and colon cancer risk and suggests that the susceptibility locus in region 8q24 is not strongly modified by various lifestyle, environmental, and demographic risk factors for colon cancer.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA. chutter@fhcrc.org
Carolyn M
CM
Hutter
Martha L
ML
Slattery
David J
DJ
Duggan
Jill
J
Muehling
Karen
K
Curtin
Li
L
Hsu
Shirley A A
SA
Beresford
Aleksandar
A
Rajkovic
Gloria E
GE
Sarto
James R
JR
Marshall
Nazik
N
Hammad
Robert
R
Wallace
Karen W
KW
Makar
Ross L
RL
Prentice
Bette J
BJ
Caan
John D
JD
Potter
Ulrike
U
Peters
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D004777:Environment; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States