HIF-1α及ERCC1基因多态性与晚期非小细胞肺癌铂类化疗近期疗效的相关性研究

Association of Genetic Polymorphisms of HIF-1α and ERCCl with the Short-term Efficacy of Platinum Drugs for Advanced Non-small Cell Lung Cancer

目的探讨缺氧诱导因子-1α(HIF-1α)C1772T(C→T,rs11549465)和切除修复交叉互补基因1(ERCC1)codon 118(C→T,rs11615)基因多态性与接受顺铂方案化疗的晚期非小细胞肺癌患者疗效的关系。方法对经病理确诊的晚期NSCLC患者68例,采用含铂方案化疗2个周期后评价疗效,采用聚合酶链-限制性片段长度多态性(PCR-restriction fragment length polymorphism,PCR-RFLP)方法检测患者外周血HIF-1αC1772T和ERCC1 codon 118进行多态性分析,比较各基因型与晚期非小细胞肺癌患者近期疗效的相关性。结果 HIF-1αC1772T基因型频率分别为:C/C型占83.82%(57/68)、C/T型占16.17%(11/68),未发现T/T型;ERCC1 codon 118基因型频率分别为:C/C型占61.76%(42/68)、C/T型占32.35%(22/68)、T/T型占5.88%(4/68)。68例患者中,完全缓解(CR)1例,部分缓解(PR)21例,疾病稳定(SD)30例,疾病进展(PD)16例;总有效率为32.35%。C/C型HIF-1αC1772T基因型患者采用铂类药物治疗的近期疗效与C/T+T/T基因型比较,差异无统计学意义(P=0.694);C/C型ERCC1基因型患者采用铂类药物治疗疗效是C/T+T/T型患者的4.125倍,差异有统计学意义(95%可信区间:1.208~14.097,P=0.019),同时携带HIF-1αC1772T C/C和ERCC1 codon 118 C/C基因型患者,对铂类药物的疗效存在一定的联合作用(P=0.001)。结论 HIF-1αC1772T和ERCC1 codon 118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 HIF-1αC1772T( C→T,rs11549465)and ERCC1 codon 118( C → T,rsl1615) with the short-term efficacy of platinum drugs for advanced non-small cell lung cancer( NSCLC). Methods The genotype s of HIF-1αC1772T and ERCC1 codon 118 were determined by PCR-RFLP in 68 patients with advanced NSCLC receiving platinum-based chemotherapy. The association of different genotypes with the short-term efficacy of platinum drugs was analyzed. Results The allele frequencies of C / C,C / T and T / T of HIF-1αC1772T were 83. 82%( 42 /68),16. 17%( 11 /68) and 0%( 0 /68),respectively,1 case achieved complete response,21 cases achieved partial response,30 cases achieved stable response and 16 cases achieved progressive disease,the overall response rate was 32. 35%. The response rate of HIF-1α C1772 T C / C allele carriers was higher than that of C / T + T / T allele carriers,but there was no statistical significance( P = 0. 694); The response rate of ERCC1 codon 118 C / C allele carriers was 4. 125-fold higher than that of C / T + T / T allele carriers,and there was significant difference( 95% confidence interval: 1. 208 ~ 14. 097,P = 0. 019) 。The two genetic polymorphisms HIF-1αC1772T C / C and ERCC1 codon 118 C / C had some synergistic effects on the efficacy of platinum drugs( P =0. 001). Conclusion The genotypes of HIF-1α and ERCC1 codon 118 maybe predictive factors for response to platinum drugs in the treatment of advanced NSCLC.