NSCLC患者CYP2D6基因多态性与吉非替尼不良反应相关性研究  

Association between CYP2D6 gene polymorphism and gefitinib adverse events in patients with NSCLC

作　　者：陈丽鹃 俞婷婷[1] 单莉[1] 韩志刚[1] CHEN Lijuan;YU Tingting;SHAN Li;HAN Zhigang(Department of Oncologic Medicine,Affiliated Tumor Hospital of Xinjiang Medical University,Xinjiang Urumqi 830000,China)

机构地区：[1]新疆医科大学附属肿瘤医院肺内一科,新疆乌鲁木齐830000

出　　处：《现代肿瘤医学》2021年第2期248-253,共6页Journal of Modern Oncology

基　　金：新疆维吾尔自治区自然科学基金资助项目(编号:2017D01C381)。

摘　　要：目的:探索口服吉非替尼片后代谢过程中不良反应发生与CYP2D6基因多态性的关系。方法:收集2016.01-2018.12于新疆医科大学附属肿瘤医院病理确诊的NSCLC患者180例,使用ARMS法行基因检测具有EGFR19del或21L858R敏感突变,并口服吉非替尼,随访过程中根据是否发生不良反应分为肝损组和非肝损组,皮疹组与非皮疹组并收集患者的外周血。应用聚合酶链式反应(polymerase chain reaction,PCR)-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)检测以上患者CYP2D6基因rs1065852位点的基因型。通过χ^2检验探究吉非替尼靶向治疗肝损害及皮疹发生的危险因素。结果:非小细胞肺癌患者CYP2D6基因rs1065852位点的基因型、肿瘤分期、基因突变类型与使用吉非替尼发生肝损害相关,CYP2D6基因rs1065852位点的基因型,肿瘤分期与吉非替尼靶向治疗皮疹发生相关,对临床用药有指导意义。结论:口服吉非替尼片的晚期非小细胞肺癌患者,CYP2D6的rs1065852位点基因多态性可预测肝功能及皮疹发生可能性。Objective:To explore the relationship between the occurrence of adverse reactions in the metabolism of oral gefitinib and the polymorphism of CYP2D6 gene.Methods:180 patients with NSCLC diagnosed in pathology department at Affiliated Tumor Hospital of Xinjiang Medical University from Jan.2016 to Dec.2018 were collected.The ARMS method was used to detect patients with EGFR19del or 21L858R sensitive mutations.During the follow-up,patients were divided into liver damage group and non-liver damage group,rash group and non-rash group according to the occurrence of adverse reactions,and peripheral blood was collected.Polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP)was used to detect the rs1065852 genotype of CYP2D6 gene in the above patients.The risk factors for the treatment of liver damage and rash occurs in gefitinib were explored by the test ofχ^2.Results:The genotype,tumor stage and gene mutation type of rs1065852 of CYP2D6 gene in patients with non-small cell lung cancer were related to liver damage caused by gefitinib,while the genotype of rs1065852 of CYP2D6 gene and tumor stage were related to the occurrence of rash,which was of guiding significance for clinical medication.Conclusion:Patients who oral gefitinib tablets with advanced non-small cell lung cancer,rs1065852 polymorphism of CYP2D6 can predict liver function and the possibility of skin rash.

关 键 词：NSCLC 吉非替尼 CYP2D6 肝损害 皮疹 

分 类 号：R734.2[医药卫生—肿瘤]