生长因子受体结合蛋白2 rs238419遗传多态性与非小细胞肺癌患者铂类药物化疗疗效的相关性研究

Correlation between genetic polymorphisms of growth factor receptor binding protein 2 and the efficacy of platinum-based chemotherapy in non-small cell lung cancer patients in Yanbian region

目的 探讨延边地区非小细胞肺癌(non-small cell lung cancer, NSCLC)患者生长因子受体结合蛋白2(growth factor receptor binding protein 2,GRB2)rs238419遗传多态性与铂类药物化疗疗效的关系。方法 将505例接受过铂类药物为基础化疗的NSCLC患者根据临床疗效分为敏感组228例和不敏感组277例。用聚合酶链反应限制性片段长度多态性检测二代测序的准确性。用SPSS 26.0软件分析NSCLC患者GRB2 rs238419位点多态性对铂类药物化疗疗效的敏感性。结果 GRB2 rs238419位点基因型符合Hardy-Weinberg遗传平衡定律。在GRB2 rs238419位点中,隐性模型下,与至少携带1个G等位基因型相比,携带AA基因型的患者对铂类化疗疗效差1.57倍(比值比=1.57,95%CI=1.01~2.43,P<0.05)。分层分析显示,携带GRB2 rs238419 AA基因型的人铂类化疗疗效差的影响因素为年龄、性别、吸烟、组织学分型及临床分期(均P<0.05)。结论 中国延边地区NSCLC患者单核苷酸多态性(GRB2 rs238419,G>A)与铂类药物化疗疗效相关。

Objective To investigate the relationship between genetic polymorphisms growth factor receptor binding protein 2(GRB2)rs238419 and the efficacy of platinum-based chemotherapy in patients with non-small cell lung cancer(NSCLC)in Yanbian region. Methods A total of 505 patients with NSCLC who had received platinum-based chemotherapy were divided into chemotherapy-sensitive group(n=228 cases) and non-sensitive group(n=277 cases) according to efficacy of solid tumors.The accuracy of second-generation sequencing was tested by polymerase chain reaction restriction fragment length polymorphisms.Sensitivity of the GRB2 rs238419 locus polymorphism to the efficacy of platinum-based chemotherapy in NSCLC patients using SPSS 26.0 statistical software. Results The GRB2 rs238419 locus genotype conforms to the Hardy-Weinberg law of genetic equilibrium. In the GRB2 rs238419 locus, patients carrying the AA genotype were 1.57-fold less effective against platinum-based chemotherapy compared to those carrying at least one G allele under the recessive model( odds ratio = 1. 57,95% CI = 1. 01-2. 43,P < 0. 05). Stratified analysis showed that the factors influencing poor efficacy of platinum-based chemotherapy in people carrying the GRB2 rs238419 AA genotype were age,sex,smoking,histological staging and pathological staging( P < 0. 05). Conclusion Single-nucleotide polymorphism( GRB2 rs238419,G > A) is significantly associated with response to platinum-based chemotherapy in NSCLC patients in Yanbian,China.