XRCC1基因单核苷酸多态性对胃癌卡培他滨联合奥沙利铂化疗敏感性研究

目的 探讨XRCC1Arg194Trp、Arg399Gln基因单核苷酸多态性对胃癌患者卡培他滨联合奥沙利铂化疗敏感性有无影响.方法 选取我院2013年1月至2014年6月经病理确诊晚期胃癌患者86例,采用卡培他滨联合奥沙利铂化疗3个周期后进行临床疗效评价.收集临床资料和外周血标本,利用TaqMan-MGB探针等位基因分型技术对XRCC1Arg194Trp、Arg399Gln进行基因分型,比较不同基因型患者的联合化疗效果.结果 86例患者中52例化疗敏感(60.5%);XRCC1Arg194Trp位点,携带Trp (Arg/Trp+Trp/Trp)基因型化疗敏感率为70.8%,Arg/Arg基因型化疗敏感率为47.4%(P=0.027);Trp基因型患者中位TTP为9.48个月,Arg/Arg基因型患者中位TTP为7.36个月(P=0.024);Arg/Arg基因耐药风险显著高于Trp基因(OR:2.84,95%CI:0.772~4.313,P=0.031);XRCC1Arg399/Arg位点,携带Arg/Arg基因化疗敏感率为72.5%,Gln (Arg/Gln+Gln/Gln)基因型化疗敏感率为42.9%(P=0.007);Arg/Arg基因中位TTP为10.26个月,Gln基因型中位TTP为8.03个月(P=0.012);Gln基因耐药风险显著高于Arg/Arg基因(OR:4.62,95%CI:1.637~7.201,P=0.012).结论 XRCC1Arg194Trp、Arg 399Gln基因单核苷酸多态性可能与卡培他滨联合奥沙利铂化疗敏感性有关.

Effect of single nucleotide polymorphism of XRCC1 gene on the sensitivity of capecitabine combined with oxaliplatin as first line chemotherapy in gastric cancer patients

Objective To investigate the effect of single nucleotide polymorphism of XRCC1Arg194Trp and Arg399Gln genes on the sensitivity of capecitabine combined with oxaliplatin as first line chemotherapy in patients with gastric cancer. Methods Eighty-six patients pathologically confirmed as advanced gastric cancer in our hospital from Jan. 2013 to Jun. 2014 were enrolled in the study, which were all treated with capecitabine combined with oxaliplatin chemotherapy. The clinical effects were evaluated after 3 cycles of treatment. The clinical data and peripheral blood sam-ples were collected, and genotyping of XRCC1Arg194Trp and Arg399Gln were performed by using TaqMan-MGB probe. Then the effects of treatment were compared between different genotypes. Results Among the 86 patients, 52 (60.5%) were sensitive to chemotherapy. At XRCC1Arg194Trp locus, the patients carrying Trp (Arg/Trp+Trp/Trp) geno-type had the sensitivity to chemotherapy of 70.8%, and the patients carrying Arg/Arg genotype had the sensitivity of 47.4%, P=0.027. The median time to progression (TTP) was 9.48 months for patients with Trp genotype and 7.36 months for those with Arg/Arg genotype, P=0.024. The risk of drug resistance for Arg/Arg genotype was significantly higher than that of Trp genotype (OR:2.84, 95%CI:0.772~4.313, P=0.031). At XRCC1Arg399/Arg locus, the patients carrying Arg/Arg genotype had the sensitivity of 72.5%, and the patients carrying Gln (Arg/Gln+Gln/Gln) genotype had the sensitivity to chemotherapy of 42.9%, P=0.007. The median TTP was 10.26 months for patients with Arg/Arg geno-type and 8.03 months for those with Gln genotype, P=0.012. The risk of drug resistance for Gln genotype was signifi-cantly higher than that of Arg/Arg genotype (OR:4.62, 95%CI:1.637~7.201, P=0.012). Conclusion Single nucleotide polymorphism of XRCC1Arg194Trp, Arg399Gln gene maybe associated with the sensitivity of capecitabine combined with oxaliplatin chemotherapy.