ERCC1和XPD单核苷酸多态性与非小细胞肺癌铂类化疗敏感性的关系

Single nucleotide polymorphisms in ERCC1 and XPD genes and sensitivity to platinum-based chemotherapy in non-small-cell lung cancer

目的:探讨DNA修复基因ERCC1 C118T和XPD Lys751Gln单核苷酸多态性与非小细胞肺癌(non-small-cell lung carcinoma,NSCLC)患者对含铂方案化疗敏感性的关系。方法:选择经病理确诊为NSCLC的患者73例,在实施化疗前采取静脉血,提取DNA,行DNA测序、用PCR-RFLP方法检测ERCC1 C118T和XPD Lys751Gln基因型。所有患者均经含铂方案化疗,观察疗效,统计临床获益率,分析NSCLC患者ERCC1和XPD单核苷酸多态性与含铂方案化疗敏感性的关系。结果:ERCC1 C118TC/C、C/T和T/T基因型临床获益率分别为94.9%、71.4%和83.8%。基因型C/C临床获益率明显高于C/T、T/T(P<0.05)。XPD Lys751Gln基因型Lys/Lys、Lys/Gln临床获益率分别为80.3%和75.0%。基因型Lys/Lys与Lys/Gln临床获益率间的差异无统计学意义(P=0.702)。未检测到XPD Gln/Gln基因型。ERCC1 C118T、XPD Lys751Gln多态之间在对含铂方案的化疗敏感性方面无协同作用(P=0.134和P=0.236)。结论:DNA修复基因ERCC1 C118T单核苷酸多态性与NSCLC含铂方案化疗的敏感性有关,可作为预测NSCLC患者铂类药物化疗敏感性的参考指标之一。

OBJECTIVE：To investigate the relationship between single nucleotide polymorphisms of DNA repair genes ERCC1 C118T and XPD Lys751Gln and sensitivity to platinum-based chemotherapy in non-small-cell lung cancer（NSCLC）. METHODS： A total of 73 patients with NSCLC were analyzed. All the patients were treated with platinum-based chemotherapy and the DNA of their peripheral blood was obtained before the therapy. ERCC1 and XPD genotypes were evaluated by DNA sequence and the polymerase chain reaction-restrictive fragment length polymorphism （PCR-RFLP） method. RESULTS： The clinical benefit rates to therapy among the patients with ERCC1 C118T C/C,C/T and T/T genotypes were 94.9%,71.4%and 83.3%,respectively . The clinical benefit rate of C/C genotype was significantly higher than C/T and T/T genotypes. There were significant differences in clinical benefit rates to platinum-based chemotherapy （P0.05）.The clinical benefit rates to therapy among the patients with XPD Lys751Gln Lys/Lys and Lys/Gln genotypes were 80.3%and 75.0%,respectively. There were no significant differences in clinical benefits to platinum-based chemotherapy（P=0.702）.The XPD Gln/Gln genotype was not detected. There were no significant differences between the genetic polymorphisms and clinical benefits to platinum-based chemotherapy on ERCC1 C118T and XPD Lys751Gln（P=0.134 and P=0.236）. CONCLUSION： Single nucleotide polymorphisms of ERCC1 C118T was associated with clinical response to platinum-based chemotherapy in NSCLC patients,suggesting the ERCC1 C118T SNP may be one of predictors for NSCLC patients who would be responsive to platinum agents.