XPA及XPG基因多态性与晚期非小细胞肺癌铂类药物化疗疗效及预后的关系

摘要

目的:研究DNA修复基因XPA A23G及XPG C46T位点基因多态性与晚期非小细胞肺癌铂类化疗疗效及预后的关系.方法:经病理学确诊的晚期非小细胞肺癌患者89例,化疗前提取其外周血DNA,用DNA测序技术检测XPA、XPG基因型,所有患者均接受2-4个周期铂类药物为基础的化疗.结果:1)89例患者中,携带XPA23A/A及A/G+G/G基因型的化疗有效率分别为47.5%和24.5%,差异有统计学意义(x2=5.137,P=0.023);携带XPG46C/C及C/T+T/T基因型的患者治疗有效率分别为47.6%、23.4%,二者间也有统计学差异(x2=5.729,P=0.017),联合分析显示A/A及C/C型化疗有效率最高,达63.0%,而A/A及C/T+T/T型最低,仅15.4%,四组间有显著统计学差异(x2=14.080,P=0.003).2)89例患者中位TTP为7个月,XPA23A/A基因型中位TTP 为11个月,A/G+G/G基因型为6个月,两者比较差异有显著性(x2=44.640,P<0.01);XPG46C/C基因型中位TTP为10个月,C/T+T/T基因型为6个月,两者也有统计学差异(x2=32.236,P<0.01).联合分析显示,XPA A/A+XPG C/C型中位TTP最长,达到11个月,而A/G+G/G及C/T+T/T基因型最短,仅有4个月,四组间差异有显著统计学意义(x2=59.295,P<0.01).结论:XPA A23G 及XPG C46T单核苷酸多态性可单独及联合用于预测晚期NSCLC病人对铂类药物的化疗疗效及TTP,初步提示可以根据患者基因型来指导个体化治疗.%Objective: To investigate the relationship between XPA, XPG single nucleotide polymorphism(SNP)and chemotherapy outcomes in advanced non-small cell lung cancer (NSCLC) patients. Methods: 89 NSCLC patients were included who were histologically diagnosed and staged as clinical stage ⅢB or Ⅳ .All patients received platinum-based doublets combination chemotherapy. We used sequencing technology to survey the distribution of XPA and XPG genotypes. Results: l)The response rate in patients with XPA23A/A genotype significantly higher than that in patients with 23A/G+G/G genotype(x2 = 5.137, P= 0.023 ),and XPG46C/C genotype higher than that in patients with 46C/T+T/T genotype (x2 =5.729, P= 0.017 ).Combined with XPA and XPG, patients with A/A and C/C had a higher response than that in patients with other genotypes.2 )The median TTP was 7 months. 11 months for XPA 23A/A genotype, and 6 months for 23A/G+G/G genotype. The differences among them were significant (x2= 44.640, P＜0.01);also, 10 months for XPG 46C/C genotype,and 6 months for 46C/T+T/T genotype. The differences among them were significant (x2 = 32.236,P＜0.01). Combined with XPA and XPG we can see that patients with A/A and C/C had a higher TTP than patients with other genotypes. Conclusions: Polymorphisms of XPA and XPG may be correlated with clinical response and TTP to platinum-based chemotherapy.