【摘要】 目的:研究DNA修复酶XRCC1基因codon194和codon399多态性与肺癌患者对铂类药物为基础的化疗敏感性的关系。方法:收集经病理学确诊的晚期肺癌112例,所有病例化疗前抽静脉血,提取白细胞DNA,用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测XRCC1基因型。所有患者均经铂类药物为基础的化疗方案治疗。结果:(1)在肺癌患者中,XRCC1194Are/Arg、Arg/Trp和Trp/Trp基因型者分别为48例(43·3%)、51例(45·9%)和12例(10·8%);XRCC1399Arg/Arg、Arg/Gln、Gln/Gln基因型者分别为65例(58·0%)、36例(32·1%)和11例(9·8%)。经化疗后,51例患者有效,总有效率45·5%。(2)XRCC1194Trp/Trp基因型者的有效率为75·0%,显著高于Arg/Arg基因型者(37·5%,χ2=5·36,P=0·0206))。前者的化疗敏感性是后者的5倍(95%CI:1·03~27·21)。同时拥有XRCC1194Trp/Trp和XRCC1399Arg/Arg基因型者的有效率为80·0%,显著高于其他基因型者(P=0·0417,OR=5·40,95%CI:0·98~38·90)。结论:XRCC1基因多态性与晚期肺癌对铂类药物为基础的化疗敏感性相关,检测XRCC1基因型可以预测晚期肺癌化疗的敏感性。更多还原

【Abstract】 Objective:To investigate the relationship between polymorphisms of DNA repair gene XRCC1 and sensitivity to platin-based chemotherapy in advanced lung cancer.Methods:112 patients with advanced lung cancer were analyzed. All patients were treated with platin-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. XRCC1 codon 194 and codon 399 genotypes were detected by PCR-RFLP method.Results:(1) Of all cases, the frequencies of XRCC1 codon 194 Arg/Arg, Arg/Trp and Trp/Trp genotype were 43.3%, 45.9% and 10.8%, while the frequencies of XRCC1 codon 399 Arg/Arg, Arg/Gln, Gln/Gln genotype were 58.0%, 32.1% and 9.8%, respectively. The overal response rate to platin-based chemotherapy in all of patients was 45.5%. (2) The response rate to therapy among patients with XRCC1 codon 194 Trp/Trp genotype (75.0%) was significantly higher compared with that among patients with the Arg/Arg genotype (37.5%,χ~2=5.36, P=0.020 6, OR=5.00, 95%CI: 1.03～27.21).The response rate to therapy among patients with XRCC1 codon 194 Trp/Trp and codon 399 Arg/Arg genotypes (80.0%) was significantly higher compared with all of other XRCC 1 genotypes (P=0.041 7, OR=5.40, 95%CI: 0.98～38.90).Conclusion:It may be suggest that the polymorphisms of the XRCC1 correlates with clinical response to platinum-based chemotherapy, and the XRCC1 genotypes detected by PCR-RFLP method can identify advanced lung cancer patients with responsive to platinum-based chemotherapy.更多还原