ERCC1和XRCC1多态与非小细胞肺癌GP方案化疗敏感性的研究  

Polymorphisms in ERCC1,XRCC1 genes and sensitivity to gemcitabine/cisplatin chemotherapy in non-small cell lung cancer

作　　者：高长明[1] 史美祺[2] 吴建中[1] 曹海霞[1] 冯继锋[2] 许林[3] 

机构地区：[1]江苏省肿瘤防治研究所/肿瘤医院流行病室,江苏南京210009 [2]江苏省肿瘤防治研究所/肿瘤医院内科,江苏南京210009 [3]江苏省肿瘤防治研究所/肿瘤医院外科,江苏南京210009

出　　处：《中华肿瘤防治杂志》2009年第1期27-30,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：江苏省科技厅社会发展重大项目基金(BS2006005)

摘　　要：目的:探讨DNA修复酶基因ER-CC1 118和XRCC1 194多态性与非小细胞肺癌(NSCLC)患者对吉西他滨/顺铂(GP)方案化疗敏感性的关系。方法:收集经病理确诊的NSCLC 57例,化疗前均抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测ER-CC1 118和XRCC1 194基因型。患者均经GP化疗方案治疗。结果:1)在NSCLC患者中,ERCC1 118C/C、C/T和T/T基因型频度分别为48.2%、51.9%和0;XRCC1 194Arg/Arg、Arg/Trp和Trp/Trp基因型频度分别为52.6%、40.4%和7.0%。化疗后,57例患者中19例有效,总有效率为33.3%。2)ERCC1 118C/C和C/T基因型者的化疗有效率分别为23.1%和46.4%,差异无统计学意义,χ2=3.164,P=0.075;XRCC1 194Trp/Trp、Trp/Arg和Arg/Arg基因型者的化疗有效率分别为50.0%、52.2%和16.7%。携带Trp等位基因者的化疗有效率(51.9%)显著高于Arg/Arg基因型者,χ2=6.41,P=0.0113。XRCC1 194与ER-CC1 118多态之间在化疗敏感性方面存在明显的交互作用,同时携带XRCC1 194Arg/Arg和ERCC1 118C/C基因型者的化疗有效率仅为6.3%(1/16),而携带XRCC1 194Trp等位基因同时携带ERCC1 118C/C、C/T基因型,其化疗的有效率均显著提高,P=0.0119和0.0076。结论:DNA修复酶基因ERCC1 118和XRCC1 194多态与NSCLC对GP方案化疗的敏感性有关,患者的基因型检测有可能作为预测NSCLC对GP方案化疗敏感性的指标。OBJECTIVE： To investigate the relationship between genetic polymorphisms in excision repair cross complementation group 1 （ERCC1） 118 and X-ray repair cross complementing group 1 （XRCC1） 194 and the response to gemcitabine/cisplatin （GP regimen） chemotherapy in non-small cell lung cancer （NSCLC）. METHODS： Fifty-seven patients with NSCLC were analyzed. All the patients were treated with GP regimen chemotherapy and their DNA of peripheral blood leukocytes was obtained before the therapy. ERCC1 and XRCC1 genotypes were detected by the PCR-RFLP method. RESULTS： 1） Of all the cases, the frequencies of ERCC1 118 C/C, C/T and T/T genotypes were 48.2%, 51.9% and 0, respectively, while the frequencies of XRCC1 194 Arg/Arg, Arg/Trp and Trp/Trp genotypes were 52.6%, 40.4% and 7.0%, respectively. The overal response rate to chemotherapy in all of the patients was 33.3%. 2） The response rate to therapy among the patients with ERCC1 118 C/C and C/T genotypeswere 23.1% and 46.4% （χ^2=3.164, P=0.075）, re spectively, and the response rate to therapy among the patients with XRCC1 194 Arg/Arg, Arg/Trp and Trp/Trp genotypes were 16.7%, 52.2% and 50.0%, respectively. The response rate to therapy among the patients with XRCC1 194 Trp allele （51.9%） was significantly higher than that among the patients with Arg/Arg genotype （16.7%）, χ^2=6.41, P=0.011 3. There was a cooperate action between ERCC1 118 and XRCC1 194 polymorphisms. The response rate to therapy among the patients with ERCC1 118 C/C and XRCC1 194 Arg/Arg genotype （6.3%） was significantly lower than that among the patients with 194 Trp allele and 118 C/C （55.6%, P=0.011 9） or 118 C/T （56.3%, P=0.007 6）. CONCLUSION： The polymorphisms of the ERCC1 and XRCC1 are associated with the clinical response to GP regimen chemotherapy in NSCLC, suggesting the ERCC1 and XRCC1 genotypes can identify advanced NSCLC patients that will be responsive to GP regimen chemotherapy.

关 键 词：癌 非小细胞肺/药物疗法 基因表达 多态现象遗传 

分 类 号：R734.2[医药卫生—肿瘤]