XPA单核苷酸多态与晚期非小细胞肺癌对铂类药物化疗敏感性的相关性研究

目的：DNA修复能力与肿瘤细胞对铂类药物的敏感性密切相关。该研究利用一种新型单核苷酸多态性（SNP）的检测方法，探讨DNA修复基因XPA的SNP与非小细胞肺癌（NSCLC）患者对顺铂（ciaplatin）或卡铂（carboplatin）为主的化疗方案敏感性的关系。方法：经病理学确诊的晚期NSCLC患者96例，采用顺铂或卡铂为主的方案化疗，2～3个周期后进行临床疗效评价。根据cDNA芯片原理制作一种目的基因芯片，利用双色荧光探针杂交进行咒蹦的A23G多态的基因分型，比较不同基因型对化疗敏感性的影响。组间比较采用χ^2检验，比值比（OR）及其95％可信区间（CI）由logistic回归模型计算。结果：成功进行基因分型，野生型、杂合型和突变型的叠加荧光分别显示为绿色、黄色和红色。携带咒蹦23A／A、A／G和G／G基因型的患者，化疗有效率（完全缓解＋部分缓解）分别为35．7％、46．9％和16．7％，差异有显著性统计学意义（P〈0．05）；携带G／G基因型患者的化疗失败风险是携带至少1个A等位基因（A／G和A/A基因型）个体的3．57倍；但G等位基因携带者的疗效与A等位基因携带者的相似，差异无统计学意义（30．9％ vs 41．7％，P=0．2045）。结论：该芯片检测方法准确、高通量且价格低廉，适用于大规模样本SNP调查；XPA基因多态与NSCLC患者对铂类药物化疗的敏感性相关。

XPA A23G polymorphism and clinical response to platin-based chemotherapy in advanced non-small cell lung cancer

Objective: DNA repair capacity is closely correlated with the sensitivity of cancer cells to platin-based chemotherapy.This study aims for a method for XPA single nucleotide polymorphism(SNP) genotyping and the association between genetic polymorphism of DNA repair gene XPA and response to cisplatin-or carboplatin-based chemotherapy of advanced non-small cell lung cancer(NSCLC).Methods: A total of 96 patients with advanced NSCLC were routinely treated by cisplatin-or carboplatin-based chemotherapy,and the clinical response was evaluated after 2-3 cycles.XPA genotypes were determined by gene-chip method using DNA samples isolated from peripheral blood collected before treatment.The odds ratios(OR) and 95% confidence intervals(CI) were computed by logistic regression.Results: Homozygous wild type,heterozygote type and homozygous mutant type yielded green,yellow and red fluorescence,respectively.The response rate to the chemotherapy in patients with the XPA 23 A/A or A/G genotype was significantly higher than in those with the G/G(P< 0.05). Conclusion: The DNA microarray-based method is accurate,high-throughput and inexpensive,suitable for SNP genotyping in a large number of individuals.Polymorphism in the XPA gene may have a significant impact on the response of NSCLC patients to platin-based chemotherapy.