ERCC1与XPD和XPA的遗传多态性对非小细胞肺癌铂类化疗敏感性预测的研究

Study on ERCC1,XPD and XPA polymorphisms for prediction of platinum-based chemotherapy sensitivity in non-small cell lung cancer

目的：分析非小细胞肺癌（NSCLC）患者ERCC1 Asn118Asn，XPD Lys751Gln和XPAA23G各基因型与以铂类为基础的化疗敏感性的关系，以及不同基因型之间疗效及生存期之间的差异。方法：采用聚合酶链反应限制性片段长度多态性（PCR—RFLP）方法分析94例NSCLC患者的基因型，并与疗效及生存期结合分析。结果：XPD Lys751Gln Lys／Lys、Lys／Gln和Gln/Gln基因型之间的中位生存期差异有统计学意义，χ^2=7．353，P＝0．007。Lys／Lys中位生存期为11个月，而Lys／Gln和Gln／Gln中位生存期为12个月，95％Cl分别为9．94～12．06和11．21～12。79。Lys／Lys、Lys／Gln和Gin／Gin各基因型对含铂类方案化疗临床获益（CR＋PR＋SD）差异无统计学意义，χ^2=2．604，P=0．272。XPA A23G AA和GG基因型及ERCC1Asn118Asn AA和TT基因型疗效之间差异无统计学意义（χ^2=1．383，P=0．550；χ^2=0．451，P=1.000）。未检测到XPA及ERCCl杂合子基因型。结论：XPD751可作为预测肺癌患者生存期的一个重要指标，为肿瘤的个体化治疗提供理论依据。

OBJECTIVE： To analyze the correlations be tween genetic polymorphisms of ERCC1Asnl18Asn, XPD Lys751Gln, XPA A23G and the clinical benefits to the platinumbased chemotherapy in NSCLC, and further investigate the effect of different genotypes for the survival and clinical out come. METHODS： The polymerase chain reaction-restrictive fragment length polymorphism （PCR RFLP） method was applied to measure the genotype in 94 patients with NSCLC, and the correlations of genetic polymorphisms with clinical benefits and survival were analyzed. RESULTS： The distributions of XPD genotypes differed significantly in median survival time （MST）（χ^2= 7. 353, P=0. 007）,Lys/Lys was 11 months, while Lys/Gln and Gin/Gin was 12 months（95~CI： 9. 94--12. 06, 11.21- 12. 79, respectively）, but there were no significant differences in clinical benefits to platinum-based chemotherapy, χ^2=2.604, P=0.272. The same statistical results were found between the genetic polymorphisms and clinical benefits on ER- CC1Asn118Asn and XPA A23G （χ^2=0. 451, P= 1. 000; 2 = 1. 383, P=0. 550; respectively）. The heterozygous genotypes of XPA and ERCC1 were not detected. CONCLUSION： XPD Lys751Gln genetic polymorphisms may be an important marker for prediction the survival in NSCLC, and can provide theoretical basis for individualized treatment.