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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。
BACKGROUND & OBJECTIVE: The chemosensitivity of tumor cells to platinum-based drugs is closely related to the DNA repair ability of individuals. In this study, the genetic polymorphisms of XPC, XPD and ERCC1, which are important members of the nucleotide excision repair system (NER) Relationship between sensitivity to platinum drugs in patients with advanced non-small cell lung cancer (NSCLC) and advanced non-small cell lung cancer (NSCLC). Methods: The clinical efficacy of 200 patients with advanced NSCLC receiving platinum-containing chemotherapy was evaluated. The genotypes of XPC-PAT, XPDLys751Gln (rs1052559) and ERCC1C8092A (rs1052559) polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-AFLP) and restriction fragment length polymorphism (RFLP) Compare the relationship between different genotypes and chemosensitivity. Results: The frequency of genotype distribution of XPC-PAT genotypes was significantly different between CR + PR group and SD + PD group (P = 0.023) The chemosensitivity of individuals with XPCLL genotype was 3.04 times higher than those with XPCSS genotype (95% CI 1.25-7.41, P = 0.015). No correlation was found between XPDLys751Gln and ERCC1C8092A polymorphisms and chemosensitivity. However, the combined analysis revealed that the three SNPs in the nucleotide excision repair system had some synergistic effect on platinum-based drug sensitivity in patients with advanced NSCLC (trend test, P = 0.021). Conclusion: The polymorphisms of XPC-PAT, XPDLys751Gln and ERCC1C8092A in the nucleotide excision repair system may be related to the sensitivity of NSCLC patients to platinum drugs.