胸苷酸合酶基因变数串联重复多态性与培美曲塞治疗晚期非小细胞肺癌疗效相关性分析  

Association between variable number of tandem repeat polymorphism of thymidylate synthase gene and e cacy of pemetrexed in the treatment of advanced non-small cell lung cancer

作　　者：胡琼[1] 李雪飞[2] 任胜祥[1] 陈晓霞[1] 唐亮[3] 张劼[3] 周彩存[1] 

机构地区：[1]同济大学附属上海市肺科医院肿瘤科,上海200433 [2]同济大学附属上海市肺科医院肿瘤免疫室,上海200433 [3]同济大学附属上海市肺科医院中心实验室,上海200433

出　　处：《肿瘤》2012年第7期539-545,共7页Tumor

摘　　要：目的:探讨胸苷酸合酶(thymidylate synthase,TS)基因5’-端非编码区(5’-untranslation region,5’-UTR)变数串联重复(variable number of tandem repeat,VNTR)多态性与培美曲塞治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)疗效的相关性。方法:回顾性分析90例晚期NSCLC患者的临床参数;抽取患者外周血标本并提取DNA,通过复合扩增荧短片段重复序列聚合酶链反应(short tandem repeat-polymerase chain reaction,STR-PCR)结合毛细血管电泳的方法检测TS基因5’-UTRVNTR的多态性。结果:TS基因5’-UTRVNTR纯合状态(2R/2R+3R/3R)与杂合状态(2R/3R+3R/4R)均与培美曲塞的临床疗效无相关性,其无进展生存期分别为112d和94d(P=0.549),疾病控制率为64.3%和67.6%(P=0.745),客观缓解率为12.5%和8.8%(P=0.591);2R多态性(2R/2R+2R/3R)和3R多态性(3R/3R+3R/4R)亦与培美曲塞的临床疗效无相关性(无进展生存期:P=0.518,疾病控制率:P=0.631,客观缓解率:P=0.541)。结论:TS基因5’-UTRVNTR多态性与培美曲塞治疗NSCLC疗效可能无相关性。Objective： To investigate the association between variable number of tandem repeat （VNTR） polymorphism in 5＇-untranslation region （5＇-UTR） of thymidylate synthase （IS） gene and the efficacy of pemetrexed-based treatment in non-small cell lung cancer （NSCLC）. Methods： Peripheral blood samples were collected from 90 patients with advanced NSCLC and the genomic DNAs were extracted from these blood samples. The VNTR polymorphism in 5＇-UTR of TS gene was detected by fluorescent labeled PCR and multiplex short tandem repeat polymerase chain reaction in combination with capillary electrophoresis. Results： The homozygosis （3R/3R and 2R/2R） and heterozygosis （2RI3R and 3R/4R） of VNTR polymorphism in 5＇-UTR of IS gene were not associated with the efficacy of pemetrexed. The progression-free survivals, disease control rates and the obJective response rates in patients harboring homozygosis （3R/3R and 2R/2R） and heterozygosis （2R/3R and 3R/4R） were 112 and 94 d （P = 0.549）, 64.3% and 67.6% （P -- 0.745）, and 12.5% and 8.8% （P -- 0.591）, respectively. The patients harboring 2R alleles had similar clinical outcomes as compared with those harboring 3R alleles （progression-free survival： P = 0.51 8; disease control rate： P = 0.631; obJective response rate： P = 0.541）. Conclusion： TS gene VNTR polymorphism may not be associated with clinical outcomes of advanced NSCLC treated with pemetrexed.

关 键 词：癌 非小细胞肺 胸苷酸合酶 抗肿瘤联合化疗方案 多态性 限制性片段长度 

分 类 号：R734.2[医药卫生—肿瘤]