摘要
背景与目的DNA修复能力与肿瘤细胞对铂类药物的敏感性密切相关。本研究探讨DNA修复基因XRCC1单核苷酸多态性与非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者对顺铂(cisplatin,DDP)或卡铂(carboplatin,CBP)为主的化疗方案敏感性的关系。方法经病理学确诊的晚期NSCLC患者105例,采用DDP或CBP为主的方案化疗,2～3个周期后进行临床疗效评价。以PCR-RFLP进行XRCC1Arg194Trp和Arg399Gln多态的基因分型,比较不同基因型对化疗敏感性的影响。比值比(OR)及其95%可信区间(CI)由logistic回归模型计算。结果携带至少一个Trp等位基因者化疗有效率为43.1%,显著高于携带Arg/Arg基因型的20.3%(OR=2.97,95%CI=1.15～7.72;P<0.05)。携带XRCC1399Arg/Arg基因型者化疗有效率为41.5%,显著高于携带至少一个Gln等位基因者的21.2%(OR=2.65,95%CI=1.03～6.87;P<0.05)。这两个多态之间存在联合作用,同时携带194Arg/Trp和399Arg/Arg基因型的患者,治疗有效率为66.7%,明显高于携带其它基因型的患者(有效率20.0%～23.1%)。结论XRCC1基因多态与NSCLC患者对铂类药物化疗的敏感性相关。
BACKGROUND &OBJECTIVE:DNA repair capacity correlated with sensitivity of cancer cells towards platin based chemotherapy. This study examined the association between genetic polymorphisms of DNA repair gene XRCC1 and response to cisplatin or carboplatin based chemotherapy of advanced non small cell lung cancer (NSCLC). METHODS: Totally 105 patients with advanced NSCLC were routinely treated with cisplatin or carboplatin based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XRCC1 genotypes were determined by PCR RFLP methods using DNA samples isolated from peripheral blood collected before treatment. The odds ratios(ORs) and 95%confidence intervals(CIs) were computed by logistic regression. RESULTS: The response rate to the chemotherapy in patients with the 194Arg/Trp or Trp/Trp genotype significantly higher than that in patients with the Arg/Arg genotype (43.1%vs. 20.3%;OR=2.97,95%CI=1.15-7.72;P< 0.05). The response rate to chemotherapy was also significantly higher in patients with the 399Arg/Arg genotype than that in patient with the Arg/Gln or Gln/Gln genotype (41.5%vs. 21.2%;OR=2.65,95%CI=1.03-6.87;P< 0.05).Furthermore, it appeared that 194Arg/Trp and 399Arg/Arg genotypes had synergic effect on the chemotherapy efficacy. Patients with both of these two polymorphisms had a response rate of 66.7%which was significantly greater than that in patients with other genotypes (response rate ranging from 20.0%to 23.1%, P< 0.001). CONCLUSION: Polymorphisms in the XRCC1 gene may have significant impact on the response of NSCLC patients to platin based chemotherapy.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2004年第8期865-868,共4页
Chinese Journal of Cancer
基金
国家十五攻关项目(No.2001BA705B10)
北京市科委重大项目(H0209-20030130)
教育部博士点基金(No.20030023014)~~
