DNA修复酶XRCC1基因多态性与晚期肺癌化疗敏感性的关系研究  

Polymorphisms in XRCC1 gene and sensitivity to platin-based chemotherapy in advanced lung cancer

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

机构地区：[1]江苏省肿瘤防治研究所肿瘤内科 [2]江苏省肿瘤防治研究所分子流行病室 [3]江苏省肿瘤防治研究所胸外科,210009

出　　处：《临床肿瘤学杂志》2006年第8期575-578,584,共5页Chinese Clinical Oncology

基　　金：江苏省科技发展计划项目(编号:BS2006005)

摘　　要：目的：研究DNA修复酶XRCC1基因codon194和codon399多态性与肺癌患者对铂类药物为基础的化疗敏感性的关系。方法：收集经病理学确诊的晚期肺癌112例，所有病例化疗前抽静脉血，提取白细胞DNA，用多聚酶链反应一限制性片段长度多态性（PCR—RFLP）分析技术检测XRCC1基因型。所有患者均经铂类药物为基础的化疗方案治疗。结果：（1）在肺癌患者中，XRCC1 194Are／Arg、Arg／Trp和Trp／Trp基因型者分别为48例（43．3％）、51例（45．9％）和12例（10．8％）；XRCC1 399Arg／Arg、Arg／Gln、Gin／Gin基因型者分别为65例（58．0％）、36例（32．1％）和11例（9．8％）。经化疗后，51例患者有效，总有效率45．5％。（2）XRCC1 194Trp／Trp基因型者的有效率为75．0％，显著高于Arg／Arg基因型者（37．5％，x^2=5．36，P=0．0206））。前者的化疗敏感性是后者的5倍（95％CI：1．03～27．21）。同时拥有XRCC1 194Trp／Trp和XRCC1 399Arg／Arg基因型者的有效率为80．0％，显著高于其他基因型者（P=0．0417，OR=5．40，95％CI：0．98～38．90）。结论：XRCC1基因多态性与晚期肺癌对铂类药物为基础的化疗敏感性相关，检测XRCC1基因型可以预测晚期肺癌化疗的敏感性。Objective：To investigate the relationship between polymorphisms of DNA repair gene XRCC1 and sensitivity to pl- atin-hased chemotherapy in advanced lung cancer. Methods： 112 patients with advanced lung cancer were analyzed. All patients were treated with platin-hased chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. XRCC1 codon 194 and codon 399 genotypes were detected by PCR-RFLP method. Results： （ 1 ） Of all cases, the frequencies of XRCC1 codon 194 Arg/Arg, Arg/Trp and Trp/Trp genotype were 43.3% , 45.9% and 10. 8% , while the frequencies of XRCC1 codon 399 Arg/Arg, Arg/Gln, Gln/Gln genotype were 58.0%, 32. 1% and 9. 8%, respectively. The overal response rate to platin-hased chemotherapy in all of patients was 45.5%. （2） The response rate to therapy among patients with XRCC1 codon 194 Trp/Trp genotype （75.0%） was significantly higher compared with that among patients with the Arg/Arg genotype （37. 5% ,X^2 = 5.36, P =0. 020 6, OR = 5.00, 95% CI： 1.03 - 27. 21 ）. The response rate to therapy among patients with XRCC1 codon 194 Trp/Trp and codon 399 Arg/Arg genotypes （ 80.0% ） was significantly higher compared with all of other XRCC 1 genotypes （ P = 0. 041 7, OR = 5.40, 95 % CI ： 0. 98 - 38.90）. Conclusion ： It may he suggest that the polymorphisms of the XRCC1 correlates with clinical response to platinum-based chemotherapy, and the XRCC1 genotypes detected by PCR-RFLP method can identify advanced lung cancer patients with responsive to platinum-based chemotherapy.

关 键 词：肺癌 XRCC1 基因多态性 化学治疗 

分 类 号：R730.54[医药卫生—肿瘤] R734.2[医药卫生—临床医学]