Genetic variants within ultraconserved elements and susceptibility to right- and left-sided colorectal adenocarcinoma.
We investigated whether single nucleotide polymorphisms within ultraconserved elements (UCEs) are associated with susceptibility to overall colorectal cancer (CRC) and susceptibility to tumor site-specific CRC. The study included 787 CRC patients and 551 healthy controls. The study comprised of a training set (520 cases and 341 controls) and a replication set (267 cases and 210 controls). We observed associations in rs7849 and rs1399685 with CRC risk. For example, a dose-dependent trend (per-allele odds ratio (OR), 0.78; 95% confidence interval (CI), 0.63-1.00; P for trend = 0.05) associated with the variant allele of rs7849 in the training set. The significant trend toward a decrease in CRC risk was confirmed in the replication set (per-allele OR, 0.72; 95% CI, 0.52-0.99; P for trend = 0.044). When stratified by tumor location, for left-sided CRC (LCRC) risk, significant association was observed for the variant-containing genotypes of rs1399685 (OR, 1.77; 95% CI, 1.02-3.06) and the risk was replicated in the replication population (OR, 2.04; 95% CI, 1.02-4.07). The variant genotypes of rs9784100 and rs7849 conferred decreased risk but the associations were not replicated. Three right-sided CRC (RCRC) susceptibility loci were identified in rs6124509, rs4243289 and rs12218935 but none of the loci was replicated. Joint effects and potential higher order gene-gene interactions among significant variants further categorized patients into different risk groups. Our results strongly suggest that several genetic variants in the UCEs may contribute to CRC susceptibility, individually and jointly, and that different genetic etiology may be involved in RCRC and LCRC.
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Moubin
M
Lin
Cathy
C
Eng
Ernest T
ET
Hawk
Maosheng
M
Huang
Anthony J
AJ
Greisinger
Jian
J
Gu
Lee M
LM
Ellis
Xifeng
X
Wu
Jie
J
Lin
D000230:Adenocarcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D017124:Conserved Sequence; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D020641:Polymorphism, Single Nucleotide