Meta association of colorectal cancer confirms risk alleles at 8q24 and 18q21.
BACKGROUND
Genome-wide association studies of colorectal cancer (CRC) have identified genetic variants that reproducibly associate with CRC. Associations of 12 single nucleotide polymorphisms at 8q24, 9p24, and 18q21 (SMAD7) and CRC were investigated in a three-center collaborative study including two U.K. case-control cohorts (Sheffield and Leeds) and a U.S. case-control study of CRC cases from high-risk Utah pedigrees.


METHODS
Our combined resource included 1,092 CRC case subjects and 1,060 age- and sex-matched controls. Meta statistics and Monte Carlo significance testing using Genie software provided a valid combined analysis of our mixed independent and related case-control resource. We also evaluated whether these associations differed by sex, age at diagnosis, family history, or tumor site.


RESULTS
At 8q24, we observed two independent significant associations at single nucleotide polymorphisms located in two different risk regions of 8q24: rs6983267 in region 3 [P(trend) = 0.01; per allele odds ratio (OR), 1.17; 95% confidence intervals (95% CI), 1.03-1.32] and rs10090154 in region 5 (P(trend) = 0.05; per allele OR, 1.24; 95% CI, 1.01-1.51). At 18q21, associations were observed in distal colon tumors but not in proximal or rectal cancers: rs4939827 (P(trend) = 0.007; per allele OR, 0.77; 95% CI, 0.64-0.93; case-case p(diff) = 0.03) and rs12953717 (P(trend) = 0.01; per allele OR, 1.27; 95% CI, 1.06-1.52). We were unable to detect any associations at 9p24 with CRC.


CONCLUSIONS
Our investigation confirms that variants across multiple risk regions of 8q24 are associated with CRC, and that associations at 18q21 differ by tumor site.
Curtin
Karen
K
Genetic Epidemiology, University of Utah School of Medicine, Salt Lake City, UT 84109, USA. karen.curtin@hsc.utah.edu
Lin
Wei-Yu
WY
George
Rina
R
Katory
Mark
M
Shorto
Jennifer
J
Cannon-Albright
Lisa A
LA
Bishop
D Timothy
DT
Cox
Angela
A
Camp
Nicola J
NJ
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009010:Monte Carlo Method; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012984:Software; D006113:United Kingdom / Q000453:epidemiology; D014589:Utah / Q000453:epidemiology