晚期非小细胞肺癌GSTP1、XRCC1基因多态性与铂类药物疗效的关系

Association of GSTP1 and XRCC1 genetic polymorphisms with the effects of platinum-based chemotherapy on advanced non-small cell lung cancer patients

目的探讨谷胱甘肽S转移酶P1（GSTP1）和X线修复交叉互补基因1（XRCC1）基因多态性与晚期非小细胞肺癌（NSCLC）患者化疗疗效的关系。方法经病理学确诊的晚期NSCLC患者94例,化疗前取静脉血采用DNA测序法检测GSTP1和XRCC1基因多态性,给予铂类为主方案化疗（顺铂75mg/m2,d1）,2~3周期后评价疗效,记录疾病进展时间（TTP）,分析GSTP1和XRCC1基因多态性与化疗疗效的关系。结果在94例晚期NSCLC患者中,携带GSTP1 A/A基因49例,G/A基因34例,G/G基因11例;携带XRCC1 G/G基因52例,G/A基因35例,A/A基因7例,均符合Hardy-Weinberg遗传平衡规律。携带GSTP1 G/A＋G/G基因型的有效率为44.44%,显著高于A/A基因型的20.41%（P〈0.05）;携带XRCC1 G/G基因型与G/A＋A/A基因型的有效率差异无统计学意义（P〉0.05）;两基因多态性的联合分析显示,同时携带GSTP1 G/A＋G/G和XRCC1 G/A＋A/A基因型的有效率最高,为66.67%,但未见统计学意义（P〉0.05）。94例患者中有5例失访,89例患者的中位TTP为6.5个月,携带GSTP1 G/A＋G/G基因型的中位TTP为8.0个月,A/A基因型为6.0个月,两者差异有统计学意义（P〈0.01）;携带XRCC1 G/G基因型的中位TTP为7.0个月,G/A＋A/A基因型为6.5个月,两者差异无统计学意义（P〉0.05）;联合分析显示同时携带GSTP1 G/A＋G/G和XRCC1G/A＋A/A基因型的中位TTP最长,为9.5个月,各组间差异有统计学意义（P〈0.01）。结论 GSTP1基因多态性与晚期NSCLC患者接受铂类为主化疗方案的疗效及预后有关,同时携带GSTP1 G/A＋G/G和XRCC1 G/A＋A/A基因型患者的化疗有效率高,预后好,但因样本量较小,需要扩大样本进一步验证。

Objective To investigate the relationship between genetic polymorphisms of GSTP1,XRCC1 and the effects of platinum-based chemotherapy on advanced NSCLC patients.Methods DNA of 94 advanced NSCLC patients was extracted from peripheral venous blood before chemotherapy.GSTP1 and XRCC1 genotypes were detected by DNA sequencing methods.The clinical response was evaluated after two or three cycles of chemotherapy and time to progression（TTP） was evaluated,and the relationship between GSTP1,XRCC1 genotypes and chemotherapeutic efficiency as well as TTP was analyzed.Results Among 94 patients,people who carrying GSTP1 A/A genotype,G/A genotype and G/G genotype were 49,34 and 11;those who carrying XRCC1 G/G genotype,G/A genotype and A/A genotype were 52,35,7.They were accarded with Hardy-Weinberg rules.Patients with GSTP1G/A＋G/G genotype showed a chemotherapeutic efficiency of 44.44% compared to patients with A/A genotype of 20.41%（P0.05）,while no statistical significant difference was found of chemotherapeutic efficiency among these patients with different XRCC1 genotypes（P0.05）.Patients with GSTP1 G/A＋G/G and XRCC1 G/A＋A/A genotype showed highest chemotherapy efficiency of 66.67%（4/6）,but no statistical significance was found（P0.05）.The median TTP was 6.5 months for the 89 patients followed-up;8.0 months for GSTP1 G/A＋G/G genotype,and 6.0 months for GSTP1 A/A genotype,and the differences among them were significant（P0.01）,while there was no correlation between XRCC1Arg399Gln gene polymorphisms and median TTP（P0.05）.Patients with GSTP1 G/A＋G/G and XRCC1 G/A＋A/A genotype had the longest median TTP of 9.5 months（P0.01）.Conclusion The GSTP1 polymorphism might be a potential predictive factor of the clinical response in patients with advanced NSCLC receiving platinum-based chemotherapy.Patients with GSTP1 G/A＋G/G and XRCC1 G/A＋A/A genotype have showed higher chemotherapy efficiency and longer median TTP,but further research is still required.