PC4基因启动子区多态性与结直肠癌发病风险的关联研究

Association between polymorphisms of human positive coactivator 4 gene promoter and risk of colorectal cancer

目的通过对PC4基因启动子区潜在功能性SNP位点与结直肠癌的发病风险的关联分析,探索PC4基因遗传变异作为结直肠癌遗传易感性分子标记的可能性。方法 (1)经生物信息学方法筛选PC4基因启动子区SNP位点;(2)采用探针法和测序法对选定SNP位点进行基因分型后于病例对照研究中作多因素Logistic回归分析。结果 (1)筛选出PC4启动子区7个潜在功能性SNP位点;(2)位点rs116123859 CC+CT基因型(OR=4.89,95%CI=1.29~18.51,P=0.020;OR_(adj)=3.31,95%CI=0.84~13.06,P_(adj)=0.087)和位点rs6891588 AG+GG基因型(OR_(adj)=1.28,95%CI=1.00~1.64,P_(adj)=0.048)与结直肠癌的发病风险有关联,但效应微弱;(3)随个体携带的"风险"倾向基因型的数量增多,结直肠癌风险也有随之增加的趋势(P_(trend)=0.004);(4)单倍型T_C_C_G_G_A_A、T_G_A_G_G_G_A患结直肠癌的风险是其他单倍型的2倍(OR分别为2.67、2.98,95%CI分别为1.78~4.02、1.46~6.04,P值分别为<0.001、0.003)。结论 PC4基因启动区单核苷酸多态性与结直肠癌的风险之间具有显著关联性,提示PC4基因启动子区多态性具有作为结直肠癌遗传易感性分子标记的潜能。

Objective To analyze the association between potential functional single nucleotide polymorphisms（SNPs） in human positive coactivator 4（PC4） gene promoter and the risk of colorectal cancer and assess the possibility of genetic variation of PC4 gene as a molecular marker of colorectal cancer predisposition. Methods The potential SNPs in PC4 gene promoter were selected using bioinformatic method,and Sanger sequencing and Taqman RT-PCR were used for genotyping these selected SNPs. Logistic regression analysis was performed to analyze the association between these SNPs and the risk of colorectal cancer in a case-control study involving 488 pathologically confirmed patients with colorectal cancer and 894 age-,gender,and residence-matched concurrent patients with non-malignant diseases. Results Seven potential SNPs in PC4 gene promoter were selected,among which the SNP sites rs116123859 AG ＋ GG（OR =4. 89,95% CI： 1. 29 - 18. 51,P = 0. 020; ORadj= 3. 31,95% CI： 0. 84 - 13. 06,Padj= 0. 087） and rs6891588 AG ＋ GG（ORadj= 1. 28,95% CI： 1. 00 - 1. 64,Padj= 0. 048） were found to be associated with the risk of colorectal cancer,but the effect was weak. The individuals carrying more risk genotypes tended to have increasing risks of colorectal cancer（Ptrend= 0. 004）. The results of haplotype analysis showed that the haplotypes T_C_C_G_G_A_A（OR = 2. 67,95% CI： 1. 78 - 4. 02,P〈0. 001） and T_G_A_G_G_G_A（OR = 2. 98,95% CI： 1. 46 - 6. 04,P〈0. 003） were associated an increased risk of colorectal cancer by2 folds compared with the other haplotypes. Conclusion SNPs of PC4 gene promoter are significantly associated with the risk of colorectal cancer and can serve as a potential molecular marker of the susceptibility to colorectal cancer.