DNA修复基因XPD XPC XRCC4基因多态性与结直肠癌易感性的关联性研究

  目的  探讨DNA修复基因XPD rs13181（codon751A/C，Lys751Gln）、rs238406（codon156C/A，Arg156Arg）、XPC rs2279017（i11C/A）和XRCC4 rs3734091（codon247T/C，Ala247Ser）的单核苷酸多态性与结直肠癌易感性的关系。  方法  采用TaqMan技术对2013年4月至2016年1月北京肿瘤医院收治的338例结直肠癌患者（病例组）和315例健康者（对照组）进行多态位点基因型的检测。  结果  XPD rs13181基因型GT和等位基因G增加个体结直肠癌的发病风险（GT>TT，adjusted OR=1.69，95%CI:1.15~2.47，P=0.007；G>T，adjusted OR=1.77，95%CI:1.19~2.64，P=0.005）；XRCC4 rs3734091基因型GT和等位基因T增加个体结直肠癌的易感性（GT>GG，adjusted OR=9.02，95%CI:5.61~14.50，P＜0.001；T>G，adjusted OR=4.06，95%CI:2.49~6.61，P＜0.001）；XPD rs13181和rs238406的单倍体型GT显著降低结直肠癌的发病风险（adjusted OR=0.39，95%CI:0.18~0.85，P=0.018）。XPCrs2279017等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=28.43，95%CI:6.85~117.95，P＜0.001）以及XPD rs13181等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=10.24，95%CI:4.69~22.35，P＜0.001）显著增加个体结直肠癌的易感性。  结论  XPD rs13181和XRCC4 rs3734091位点的多态性与结直肠癌的易感性相关。 

Genetic polymorphisms of DNA repair genes XPD,XPC, and XRCC4 in relation to colorectal cancer susceptibility

Objective:To investigate the association of XPD rs13181 (codon751A/C, Lys751Gln), rs238406 (codon156C/A, Arg156Arg), XPC rs2279017 (i11C/A), and XRCC4 rs3734091 (codon247T/C, Ala247Ser) polymorphisms with colorectal cancer (CRC) susceptibility. Methods:A total of 338 patients with CRC who were treated at the Beijing Cancer Hospital from April 2013 to January 2016 (case group) and 315 healthy controls (control group) were genotyped using TaqMan technology. Results:The genotype GT and G alleles of XPD rs13181 increased the risk of CRC (GT>TT, adjusted OR=1.69, 95%CI=1.15-2.47, P=0.007;G>T, adjusted OR=1.77, 95%CI=1.19-2.64, P=0.005). The genotype GT and T alleles of XRCC4 rs3734091 increased the susceptibility of CRC (GT>GG, adjusted OR=9.02, 95%CI=5.61-14.50, P<0.001;T>G, adjusted OR=4.06, 95%CI=2.49-6.61, P<0.001). Analyses of XPD rs13181 and rs238406 indicated that the haplotype GT significantly decreased the risk of CRC (adjusted OR=0.39, 95%CI=0.18-0.85, P=0.018). Moreover, the combinations of the XPC rs2279017 G allele and the XRCC4 rs3734091 T allele (adjusted OR=28.43, 95%CI=6.85-117.95, P<0.001) and the XPD rs13181 G allele and the XRCC4 rs3734091 T allele (adjusted OR=10.24, 95%CI=4.69-22.35, P<0.001) exhibited significantly increased CRC risk. Conclusion:The polymorphisms of XPD rs13181 and XRCC4 rs3734091 increased the risk of CRC.