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XRCC1 单核苷酸多态性预测晚期NSCLC铂类药物化疗的敏感性

Single Nucleotide Polymorphisms in XRCC1 and Clinical Response to Platin-based Chemotherapy in Advanced Non-small Cell Lung Cancer

  • 摘要: 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。

     

    Abstract: 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.

     

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