PDF(Pubmed)
Abstract：
Objective: The purpose of this study was to investigate the associations of genetic variants in double-strand break (DSB) repair pathway genes with prognosis in patients with lung cancer treated with platinum-based chemotherapy. Methods: Three hundred ninety-nine patients with lung cancer who received platinum-based chemotherapy for at least two cycles were included in this study. A total of 35 single nucleotide polymorphisms (SNPs) in DSB repair, base excision repair (BER), and nucleotide excision repair (NER) repair pathway genes were genotyped, and were used to evaluate the overall survival (OS) and the progression-free survival (PFS) of patients who received platinum-based chemotherapy using Cox proportional hazard models. Results: The PFS of patients who carried the MAD2L2 rs746218 GG genotype was shorter than that in patients with the AG or AA genotypes (recessive model: p = 0.039, OR = 5.31, 95% CI = 1.09-25.93). Patients with the TT or GT genotypes of TNFRSF1A rs4149570 had shorter OS times than those with the GG genotype (dominant model: p = 0.030, OR = 0.57, 95% CI = 0.34-0.95). We also investigated the influence of age, gender, histology, smoking, stage, and metastasis in association between SNPs and OS or PFS in patients with lung cancer. DNA repair gene SNPs were significantly associated with PFS and OS in the subgroup analyses. Conclusion: Our study showed that variants in MAD2L2 rs746218 and TNFRSF1A rs4149570 were associated with shorter PFS or OS in patients with lung cancer who received platinum-based chemotherapy. These variants may be novel biomarkers for the prediction of prognosis of patients with lung cancer who receive platinum-based chemotherapy.
摘要：
目的：本研究的目的是探讨双链断裂（DSB）修复途径基因的遗传变异与铂类化疗患者预后的关系。方法：本研究纳入了79例接受铂类化疗至少2个周期的肺癌患者。共有35个单核苷酸多态性（SNPs）在DSB修复中，碱基切除修复（BER），和核苷酸切除修复（NER）修复途径基因进行基因分型，使用Cox比例风险模型评估接受铂类化疗患者的总生存期(OS)和无进展生存期(PFS).结果：携带MAD2L2rs746218GG基因型的患者的PFS短于AG或AA基因型的患者（隐性模型：p=0.039，OR=5.31，95％CI=1.09-25.93）。TNFRSF1Ars4149570的TT或GT基因型患者的OS时间比GG基因型患者短（优势模型：p=0.030，OR=0.57，95％CI=0.34-0.95）。我们还调查了年龄的影响，性别,组织学,吸烟,舞台,肺癌患者SNP与OS或PFS之间的相关性和转移。在亚组分析中，DNA修复基因SNP与PFS和OS显着相关。结论：我们的研究表明，在接受铂类化疗的肺癌患者中，MAD2L2rs746218和TNFRSF1Ars4149570的变异与较短的PFS或OS相关。这些变异可能是预测接受铂类化疗的肺癌患者预后的新型生物标志物。
