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目的:研究DNA修复基因XPAA23G及XPGC46T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,XPAA/A+XPGC/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:XPAA23G及XPGC46T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 study the relationship between the polymorphisms of XPAA23G and XPGC46T DNA repair genes and the efficacy and prognosis of advanced non-small cell lung cancer with platinum-based chemotherapy. Methods: Eighty-nine patients with pathologically diagnosed advanced non-small cell lung cancer were recruited. DNA was extracted from peripheral blood before chemotherapy. XPA and XPG genotypes were detected by DNA sequencing. All patients received 2-4 cycles of platinum-based drugs Chemotherapy. Results: 1) Among the 89 patients, the efficacies of carrying XPA23A / A and A / G + G / G genotypes were 47.5% and 24.5%, respectively, with statistical significance (x2 = 5.137, P = 0.023) The effective rates of patients with XPG46C / C and C / T + T / T genotypes were 47.6% and 23.4%, respectively. There was also a significant difference between them (x2 = 5.729, P = 0.017) And C / C type chemotherapy had the highest rate of 63.0%, while the A / A and C / T + T / T type was the lowest, only 15.4%. There was a statistically significant difference between the four groups (x2 = 14.080, P = 0.003) . 2) The median TTP of 89 patients was 7 months, the median TTP of XPA23A / A genotype was 11 months, and the genotype of A / G + G / G was 6 months. The difference was significant (x2 = 44.640, P <0.01). The median TTP of XPG46C / C genotype was 10 months and the C / T + T / T genotype was 6 months. There was also a significant difference between the two genotypes (x2 = 32.236, P <0.01). The combined analysis showed that the median TTP of XPAA / A + XPGC / C type was the longest, reaching 11 months, while the shortest of A / G + G / G and C / T + T / T genotypes were only 4 months and 4 There was significant difference between groups (x2 = 59.295, P <0.01). Conclusion: XPAA23G and XPGC46T single nucleotide polymorphisms can be used alone or in combination to predict the response to chemotherapy and TTP in advanced NSCLC patients. It is suggested that individualized therapy can be guided according to patient’s genotype.