DNA损伤修复基因XRCC1和XPD遗传多态与晚期非小细胞肺癌对铂类药物的敏感性  

XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer

作　　者：袁芃[1] 缪小平[2] 张雪梅[2] 王中华[1] 谭文[2] 孙燕[1] 张湘茹[1] 徐兵河[1] 林东昕[2] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院内科,北京100021 [2]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院病因及癌变研究室,北京100021

出　　处：《中华肿瘤杂志》2006年第3期196-199,共4页Chinese Journal of Oncology

基　　金："十五"国家科技攻关计划项目(2001BA705B10);首都医学发展科研基金资助项目(20032009);北京市自然科学基金资助项目(7013035);国家杰出青年科学基金资助项目(39825122);教育部博士点基金资助项目(20030023014)

摘　　要：目的探讨DNA损伤修复基因XRCC1和XPD的遗传多态与晚期非小细胞肺癌(NSCLC)对以铂类为主化疗药物敏感性的关系。方法以聚合酶链反应(PCR)结合限制性片段长度多态性(RFLP),检测200例以顺铂(DDP)或卡铂(CBP)为主要化疗方案的NSCLC患者XRCC1Arg194Trp和XPDLys751Gln多态基因型,并比较不同基因型与化疗敏感性的关系。结果化疗总有效(CR+PR)率为36.0%,其中CR1例,PR71例,SD94例,PD34例。携带XRCC1第194位密码子Arg/Trp或Trp/Trp基因型的个体化疗敏感性是XRCC1第194位密码子Arg/Arg基因型携带者的2.48倍(95%CI为1.36～4.51,P=0.003);未发现XPDLys751Gln多态与化疗敏感性的相关性。联合分析这两个遗传多态发现,XRCC1Arg194Trp和XPDLys751Gln多态在NSCLC对铂类药物敏感性中存在一定的联合作用(趋势检验,P=0.004)。结论XRCC1Arg194Trp和XPDLys751Gln遗传多态可能与NSCLC铂类药物敏感性有关。Objective DNA repair system plays an important role in tumor sensitivity to platinumbased chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses. Results The overall response rate （ CR ＋ PR ） was 36. 0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype （adjusted OR, 2. 48; 95% CI, 1.36-4. 51, P = 0.003）. However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant （P = 0. 004）. Conclusion Those results suggest that the XRCC1 Arg194Trp and XPD Lys751 Gin genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.

关 键 词：基因遗传变异 XRCC1 XPD 非小细胞肺癌 化疗敏感性 

分 类 号：R734.2[医药卫生—肿瘤]