晚期非小细胞肺癌患者XPG基因及MDR1基因单核苷酸多态性与铂类化疗疗效的相关性

The Relationship between the Polymorphisms of Gene XPG and MDR1 and the Responsiveness of Advanced Non-small Cell Lung Cancer to Platinum-based Chemotherapy

目的探讨DNA修复基因XPG以及多药耐药基因MDR1的单核苷酸多态性与晚期非小细胞肺癌患者对铂类为主的化疗方案敏感性的关系。方法经病理确诊的晚期NSCLC患者101例,采用DDP为主的化疗方案,化疗2～3个周期后进行临床疗效评价。以PCR-RLFP方法进行XPG、MDR-1的基因型分析,比较不同基因型对化疗敏感性的影响。结果携带MDR1-3435等位基因C/C的患者的化疗有效率为57.8%,显著高于至少携带1个T等位基因的26.8%(OR=0.272,95%CI=0.117～0.635,P(0.05));携带MDR1-2677至少1个T等位基因的患者的化疗有效率12.8%要显著低于其他基因型患者的58.1%(OR=17.999,95%CI=4.938～65.599,P(0.01);而XPG各基因型与化疗敏感性的关系没有显著性的差异。结论MDR1基因多态性与NSCLC患者对铂类药物的化疗敏感性相关,基因XPG的多态性是否与铂类药物化疗的敏感性是否具有相关性尚需进一步的研究。

Objective To investigate the relationship between genetic polymorphisms of MDR1 and XPG and response rate of platinum-based chemotherapy on non-small-cell lung cancer. Methods 101 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XPG and MDR1 genotypes were determined by PCR-RFLP. Results The response rate to the chemotherapy in patients with the allele MDR1-3435 C/C was significantly higher than that in patients with the T/C or T/T genotype（57.8% vs. 26.8% ; OR = 0. 272,95% CI = 0. 117 0.635 ,P 〈 0.05 ） ; The response rate to the chemotherapy in patients with MDR1-2677 T/T or G/T genotype was significantly lower than that in patients with other genotypes （12.8% vs. 58.1%; OR = 17. 999,95% CI = 4. 938 -65. 599, P 〈 0.01 ）; While there was no statistically significant association between the XPG polymorphisms and response rate to the chemotherapy. Conclusion Genetic polymorphisms of MDR1 have significant impact on response rate in NSCLC patients treated with platinumbased chemotherapy. Further study is necessary to confirm whether there is association between the polymorphisms of XPG gene and response to platinum-based chemotherapy.