CYP3A4基因18B位点多态性与晚期EGFR基因突变NSCLC患者疗效及不良反应的关系  

Relationships of CYP3A4 gene 18B polymorphisms with efficacy and adverse reactions in advanced NSCLC patients with EGFR gene mutation

作　　者：程艳芳[1] 费晶[1] 王艳娜[1] 王慧[1] 孟玲利[1] 巩平[1] CHENG Yanfang;FEI Jing;WANG Yanna;WANG Hui;MENG Lingli;GONG Ping(The First Affiliated Hospital of Shihezi University Medical College, Shihezi 832000, China)

机构地区：[1]石河子大学医学院第一附属医院,新疆石河子832000

出　　处：《山东医药》2017年第37期1-4,共4页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(81560381);吴阶平研究课题资助项目(320.6750.14269)

摘　　要：目的探讨细胞色素3A4(CYP3A4)基因18B位点(CYP3A4*18B)多态性与表皮生长因子受体(EGFR)基因突变晚期非小细胞肺癌(NSCLC)患者疗效及不良反应的关系。方法选择EGFR基因突变晚期初治NSCLC患者44例,口服EGFR酪氨酸激酶抑制剂(EGFR-TKI)吉非替尼片250 mg,1次/d;或厄洛替尼片150 mg,1次/d。直至患者病情进展或无法耐受不良反应而停药。治疗前采用PCR及直接测序法检测CYP3A4*18B的基因突变状态,比较突变型和野生型患者疗效(客观缓解率、疾病控制率)及不良反应的差异。结果 CYP3A4*18B基因突变频率为36.4%(16/44),野生型纯合子占63.6%(28/44),突变型杂合子占34.1%(15/44),突变型纯合子占2.3%(1/44)。野生型与突变型患者疗效比较差异无统计学意义(P均>0.05),野生型患者皮疹发生率高于突变型患者(P<0.05)。结论 CYP3A4*18B的多态性与晚期EGFR基因突变NSCLC患者的EGFR-TKI疗效无关,与药物不良反应有关。To explore the relationships of cytochrome3A4(CYP3A4)gene18B polymorphisms(CYP3A4*18B)on the efficacy and adverse reactions in advanced non small cell lung cancer(NSCLC)patients with EGFR gene mutation.MethodsForty four patients with newly diagnosed advanced NSCLC were chosen and treated with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR TKI)gefitinib250mg,once a day,or erlotinib150mg,once a day;when the patients could not tolerate the adverse reactions,we stop the medication.PCR and the direct sequencing were carried out to determine the mutations of CYP3A4*18B before treatment,and then we compared the efficacy(objective response rate,disease control rate)and adverse reactions between mutant type and wild type patients.ResultsThe mutation frequency of CYP3A4*18B gene was36.4%(16/44),among which wild type homozygote accounted for63.6%(28/44),mutant heterozygote accounted for34.1%(15/44),and mutant homozygote accounted for2.3%(1/44).There was no significant difference in efficacy of EGFR TKI between wild type and mutant type patients(all P>0.05).Patients with CYP3A4*18B gene wild type had a higher incidence of rash than that of the mutant type(P<0.05).Conclusion The polymorphism of CYP3A4gene18B is not related to the efficacy of EGFR TKI for advanced NSCLC patients with EGFR gene mutation,but is related to the adverse reactions of drugs.

关 键 词：非小细胞肺癌 细胞色素3A4 表皮生长因子 基因多态性 酪氨酸激酶抑制剂 治疗结果 不良反应 

分 类 号：R734.2[医药卫生—肿瘤]