| Summary: | Objective To investigate the association of single nucleotide polymorphisms (SNPs) of homologous recombination repair (HRR) pathway genes with the genetic susceptibility of colorectal cancer (CRC) in Chinese population. Methods Bioinformatics database analysis combined with literature screening was used to identify the key genes involved in the HRR pathway. Following a pathway-based case-control study design, 413 patients with CRC and 1 671 cancer-free controls were recruited from 3 affiliated hospitals of the Army Military Medical University. TagSNPs of the selected genes and 50 kb of their upstream and downstream regions were genotyped using ILLUMINA human genome chip. Conditional logistic regression analysis was used to evaluate the association between the SNPs and the risk of CRC. Results Seventeen key genes in the HRR pathway were selected based on literature screening and bioinformatics database analysis. Sixteen of the total of 2207 genotyped SNPs were found significantly associated with the risk of CRC, among them the allele A at rs11226 of RAD52 3'-UTR was associated with an 1.4-fold higher risk of CRC than the allele G (OR=1.42, 95% CI: 1.22~1.66, P=6.67×10-6), and the allele G at rs75893366 of CRTC3-AS1 gene was associated with a 0.43-fold lower risk of CRC than allele A (OR=0.43, 95% CI: 0.25~0.74, P=1.81×10-3). But after Bonferroni correction, only the SNP of rs11226 showed significant differences in both male and female patients in stratified analysis. Conclusion The 17 SNPs of the key genes in the HHR pathway are significantly associated with the risk of CRC, suggesting that the variations in HHR pathway genes contribute to the genetic susceptibility of CRC.
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