核苷酸切除修复系统基因遗传多态与晚期非小细胞肺癌患者铂类药物敏感性关系

背景与目的:肿瘤细胞对铂类药物的化疗敏感性与个体的DNA损伤修复能力关系密切,本研究探讨核苷酸切除修复系统(nucleotideexcisionrepair,NER)的重要成员XPC、XPD和ERCC1基因的遗传多态与晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)患者对铂类药物敏感性的关系。方法:对接受含铂类药物化疗的200例晚期NSCLC患者进行临床疗效评价。以聚合酶链-扩增片段长度多态性(PCR-AFLP)和限制性片段长度多态性(RFLP)的方法检测XPC-PAT、XPDLys751Gln(rs1052559)和ERCC1C8092A(rs1052559)多态的基因型,比较不同基因型与化疗敏感性的关系。结果:结合疗效情况,XPC-PAT遗传多态各基因型在化疗有效组(CR PR)和无效组(SD PD)中的分布频率差异有显著性(!2检验,P=0.023),携带XPCLL基因型个体的化疗敏感性是XPCSS基因型携带者的3.04倍(95%CI为1.25～7.41,P=0.015)。没有发现XPDLys751Gln和ERCC1C8092A多态与化疗敏感性的相关性。但联合分析后发现,核苷酸切除修复系统的这三个遗传多态在晚期NSCLC患者对铂类药物敏感性中存在一定的联合作用(趋势检验,P=0.021)。结论:核苷酸切除修复系统中XPC-PAT、XPDLys751Gln和ERCC1C8092A遗传多态可能与NSCLC患者对铂类药物敏感性相关。

Correlation of genetic polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer patients to platinum-based chemotherapy

BACKGROUND & OBJECTIVE: DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. This study was to examine the correlations of polymorphisms in nucleotide excision repair system to sensitivity of advanced non-small cell lung cancer (NSCLC) to platinum-based chemotherapy. METHODS: Treatment outcomes of 200 advanced NSCLC patients, treated with platinum-based chemotherapy, were evaluated. XPC-PAT, XPD Lys751Gln (rs1052559), and ERCC1 C8092A (rs1052559) were genotyped by polymerase chain reaction-amplified fragment length polymorphism (PCR-AFLP) or PCR-restrictive fragment length polymorphism (PCR-RFLP) methods in the 200 patients. Unconditional logistic regression model was used to analyze the correlation of genetic polymorphisms to clinical response. RESULTS: The distributions of XPC-PAT genotypes differed significantly between response group (complete response + partial response) and un-response group (stable disease + progressive disease)(P=0.023). The XPC LL genotype carriers had higher response rate than the SS genotype carriers (OR=3.04; 95% CI=1.25-7.41, P= 0.015). The XPD Lys751Gln and ERCC1 C8092A polymorphisms were not found to be associated with platinum-based chemotherapy. However, these 3 genetic polymorphisms in nucleotide excision repair system had interaction in the drug sensitivity (P=0.021). CONCLUSION: The genetic polymorphisms of XPC-PAT, XPD Lys751Gln, and ERCC1 C8092A in nucleotide excision repair system may be associated with sensitivity of NSCLC patients to platinum-based chemotherapy.