XRCC1 单核苷酸多态性预测晚期NSCLC铂类药物化疗的敏感性

 目的 研究XRCC1单核苷酸多态性与晚期非小细胞肺癌（nowsmallcelllungcancer，NSCLC）对以顺铂（cisplatin，DDP）或卡铂（carDoplatin，CBP）为基础药物的化疗敏感性的关系。方法 经病理学确诊的晚期NSCLC患者97例，采用DDP或CBP为基础药物的方案化疗，3个周期后进行疗效评价。以聚合酶链反应（PCR）结合限制性片段长度多态性（RFLP）检测RiCelArg194Trp和Arg399G1n基因型，并比较基因型与化疗敏感性的关系。结果 （1）携带RiCel194Arg／Trp的患者有效率高于携带Arg／Arg、Trp／Trp基因型的患者（P〈0．05）；携带至少一个Trp等位基因基因型患者的化疗敏感性是携带Arg／Arg基因型的3．4倍（OR=3．39，95％，CI=1．3248．70，P〈0.05）。（2）携带RiCel399Arg／Arg、Arg／G1n、Gin／Gin基因型患者的有效率分别为36．4％、22．9％、28．6％，差异无统计学意义（P〉0.05）。尚未发现RiCelArg194Trp和Arg399Gln基因多态性存在联合作用。结论 XRCClArg194Trp单核苷酸多态性可能与晚期NSCLC对铂类药物的化疗敏感性相关。

Single Nucleotide Polymorphisms in XRCCI and Clinical Response to Platin-based Chemo- therapy in Advanced Non-small Cell Lung Cancer

Objective 　This study examined the association between genetic polymorphisms of XRCC1 and response to cisplatin- or carboplatin- based chemotherapy of advanced non-small cell lung cancer (NSCLC) . Methods 　Totally 97 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin- based chemotherapy , and clinical response was evaluated af ter 3 cycles. XRCC1 genotypes were determined by PCR-RFLP methods using DNA samples isolated from peripheral blood collected before treatment . Results 　(1) The response rate to the chemotherapy in patients with the XRCC1 194Arg/Trp genotype significantly higher than that in patient s with the Arg/ Arg、Trp/ Trp genotype ( P < 0. 05) ;The XRCC1 194 Trp allele carriers had higher response rate than the subjects with the Arg/ Arg genotype (adjusted OR = 3. 39 ,95 % CI = 1. 32～8. 70 , P < 0. 05) . There was no difference of the response rate (34. 6 %、27. 5 % , 20. 0 %) to chemotherapy with the 399 Arg/ Arg、Arg/ Gln、Gln/Gln gene type ( P >0. 05) . Furthermore , it did not appear that 194Arg/ Trp and 399Arg/ Arg genotypes had synergic effect on the chemotherapy efficacy. Conclusion 　Polymorphisms in the XRCC1 Arg194 Trp may have significant impact on the response of NSCLC patient s to platin-based chemotherapy.