BAG-1和ERCC1基因多态性与晚期非小细胞肺癌患者铂类药物敏感性的关系  

The association of genetic polymorphisms of BAG-1 and ERCC1 with the clinical response to platinum drugs in patients with advanced non-small cell lung cancer

作　　者：王亚帝[1] 成健[1] 陈君臣[1] 王月[1] 哈敏文[1] 

机构地区：[1]辽宁医学院附属第一医院肿瘤科,锦州121000

出　　处：《肿瘤》2011年第9期824-829,共6页Tumor

基　　金：辽宁省教育厅科研资助项目(编号:L2010286)

摘　　要：目的:探讨Bcl-2结合抗凋亡基因1(Bcl-2associated athanogene1,BAG-1)codon324(C→T,rs11551682)和切除修复交叉互补基因1(excision repair cross-complementing group1,ERCC1)codon118(C→T,rsl1615)基因多态性与晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者对铂类药物敏感性的关系。方法:以聚合酶链-限制性片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)方法检测142例接受铂类药物化疗的晚期NSCLC患者的BAG-1codon324基因型和ERCC1codon118基因型,比较不同基因型与化疗敏感性的关系。结果:BAG-1codon324基因型频率分别为C/C占77.46%(110/142),C/T占22.54%(32/142),未发现T/T。142例患者中,完全缓解4例,部分缓解42例,疾病稳定55例,疾病进展41例;总有效率为32.39%。BAG-1codon324C/C基因型患者对顺铂类药物的敏感性是C/T基因型患者的2.852倍(95%可信区间:1.133～7.182,P=0.026),且BAG-1codon324C/C基因型与C/T基因型患者的中位无进展生存期差异有统计学意义(分别为5.7和5.3个月,P=0.002)。携带BAG-1codon324C/C和ERCC1codon118C/C基因型,对铂类药物的敏感性存在一定的联合作用(P=0.005)。结论:BAG-1codon324和ERCC1codon118基因型可能是晚期NSCLC患者铂类药物敏感性的预测因子。Objective：To investigate the association of genetic polymorphisms of Bcl-2 associated athanogene 1（BAG-1） codon 324（C→T,rs11551682） and excision repair cross-complementing group 1（ERCC1） codon 118（C→T,rsl1615） with the response to platinum drugs in patients with advanced non-small cell lung cancer（NSCLC）.Methods：The genotypes of BAG-1 codon 324 and ERCC1codon 118 were determined by PCR-restriction fragment length polymorphism（PCR-RFLP） method in 142 patients with advanced NSCLC receiving platinum-based chemotherapy.The association of different genotypes with the clinical response to platinum drugs was analyzed.Results：The allele frequencies of C/C,C/T and T/T of BAG-1 codon 324 were 77.46%（110/142）,22.54%（32/142） and 0%（0/142）,respectively.Of 142 patients,4 achieved complete response,42 achieved partial response,55 achieved stable response,and 41 achieved progressive disease;the overall response rate was 32.39%.The response rate of BAG-1 codon 324 C/C allele carriers was 2.852-fold higher than that of C/T allele carriers（95% confidence interval：1.133-7.182;P=0.026）,and there was a significant difference in progression-free survival between patients carrying with BAG-1 codon 324 C/C and C/T（5.7 months vs 5.3 months,P=0.002）.The two genetic polymorphisms — BAG-1 codon 324 C/C and ERCC1 codon 118 C/C had some synergistic effects on the response to platinum drugs（P=0.005）.Conclusion：The genotypes of BAG-1 codon 324 and ERCC1 codon 118 may be predictive factors for response to platinum drugs in the treatment of advanced NSCLC.

关 键 词：癌 非小细胞肺 抗肿瘤联合化疗方案 多态性 单核苷酸 Bcl-2结合抗凋亡基因1 切除修复交叉互补基因1 

分 类 号：R734.2[医药卫生—肿瘤]