UGT1A1基因多态性与小细胞肺癌患者使用伊立替康所致毒性和生存期之间的相关性分析  

Association analysis of UGT1A1 gene polymorphism with toxicity and survival in patients with small cell lung cancer treated with irinotecan

作　　者：侯文洁[1] 周秋云[1] 张宇[2] 王洁[1] 丁红梓[1] 张亮[1] HOU Wenjie;ZHOU Qiuyun;ZHANG Yu;WANG Jie;DING Hongzi;ZHANG Liang(Departemt of Pharmacy,Nanjing Chest Hospital/Affiliated Nanjing Brain Hospital,Nanjing Medical University,Nanjing Jiangsu 210029,China;Department of Respiratory,Nanjing Chest Hospital/Affiliated Nanjing Brain Hospital,Nanjing Medical University,Nanjing Jiangsu 210029,China)

机构地区：[1]南京市胸科医院/南京医科大学附属脑科医院药学部,江苏南京210029 [2]南京市胸科医院/南京医科大学附属脑科医院呼吸内科,江苏南京210029

出　　处：《临床肺科杂志》2023年第9期1297-1303,1320,共8页Journal of Clinical Pulmonary Medicine

基　　金：江苏省研究型医院学会精益化用药-石药专项科研基金(No.JY202125);南京市医学科技发展项目(No.GBX21296);南京市医学科技发展项目(No.GAX22280)。

摘　　要：目的评估使用伊立替康(CPT-11)的小细胞肺癌(SCLC)患者中尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)的多态性与临床结局的关联性。方法观察77例初治SCLC患者接受CPT11-铂双药治疗,评估指标的血液毒性、胃肠道毒性、缓解率和总生存期。使用非扩增荧光原位杂交法检测UGT1A1*28和UGT1A1*6的基因型,分类为纯合野生型、杂合突变体或纯合突变体。结果在77名患者中,UGT1A1*6位点多态性的频率为67名(87.0%)纯合野生型,7名(9.1%)杂合突变型,3名(3.9%)纯合突变体;对于UGT1A1*28,32例(41.6%)纯合野生型,33例(42.9%)杂合突变型,12例(15.5%)纯合突变体。UGT1A1*6存在突变会使严重(≥3级)腹泻和粘膜炎出现的更频繁。在多变量逻辑回归分析中,UGT1A1*6的突变状态是与粘膜炎和严重腹泻相关的唯一变量。UGT1A1*28发生突变的患者OS更好,在多变量Cox比例风险分析中,UGT1A1*28的发生突变与更好的OS独立相关,而无影像学改善、中度/重度吸烟和年龄增加与较差的OS相关。结论在使用CPT-11治疗的SCLC患者中,UGT1A1*6和UGT1A1*28的基因多态性分别与胃肠道毒性增加和OS改善相关。Objective To evaluate the association of UGT1A1 polymorphisms and clinical outcomes in small cell lung cancer(SCLC)patients treated with Irinotecan(CPT-11).Methods Seventy-seven patients with newly diagnosed SCLC who received CPT-11-platinum double-drug therapy were observed.The evaluation indicators were blood toxicity,gastrointestinal toxicity,remission rate,and overall survival.Genotypes of UGT1A1*28 and UGT1A1*6 were detected using non-amplified fluorescence in situ hybridization and classified as homozygous wild-type(W/W),heterozygous mutant(W/M)or homozygous mutant(M/M).Results Among 77 patients,the frequency of UGT1A1*6 locus polymorphism was 67(87.0%)homozygous wild type,7(9.1%)heterozygous mutant,and 3(3.9%)homozygous mutant;For UGT1A1*28,32 cases(41.6%)were homozygous wild type,33 cases(42.9%)were heterozygous mutant,and 12 cases(15.5%)were homozygous mutant.The presence of mutations in UGT1A1*6 results in a more frequent occurrence of severe(≥grade 3)diarrhea and mucositis.In multivariate logistic regression analysis,the mutational status of UGT1A1*6 was the only variable associated with mucositis and severe diarrhea.Patients with mutations in UGT1A1*28 had better OS,and in multivariate Cox proportional risk analysis,mutations in UGT1A1*28 were independently associated with better OS,while lack of imaging changes,moderate/heavy smoking,and increasing age were associated with worse OS.Conclusion In SCLC patients treated with CPT-11,UGT1A1*6,and UGT1A1*28 gene polymorphisms are associated with increased gastrointestinal toxicity and improved OS,respectively.

关 键 词：小细胞肺癌 尿苷二磷酸葡萄糖醛酸转移酶1A1 伊立替康 毒性 生存期 

分 类 号：R734.2[医药卫生—肿瘤]