胸苷酸合成酶基因多态性与晚期胃癌化疗敏感性的关系  

Relationship of polymorphism in the 5-untranslated region of thymidylate synthase gene and sensitivity of stomach cancer to fluoropymidine-based chemotherapy

作　　者：杨磊[1] 肖明兵[2] 倪润洲[2] 谭清和[1] 魏金芝[1] 王建红[1] 徐小红[1] 

机构地区：[1]南通大学附属肿瘤医院,226361 [2]南通大学附属医院消化病研究室

出　　处：《江苏医药》2009年第8期887-889,共3页Jiangsu Medical Journal

基　　金：南通市科技局课题通卫规财(2006-29)

摘　　要：目的研究胸苷酸合成酶(TS)基因5′端非编码区(UTR)多态性与晚期胃癌对氟尿嘧啶(5-FU)化疗敏感性的关系。方法经病理学确诊的晚期胃癌56例,化疗前抽静脉血,提取白细胞DNA,用PCR技术检测TS5′-UTR基因型。所有患者均经5-FU为基础的化疗方案治疗。以实体瘤疗效评定标准和毒性评定标准评价疗效和毒性。结果56例胃癌患者中,TS5′-UTR基因型分2R/2R、2R/3R、3R/3R,基因型频率分别为5.4%、42.8%和51.8%,化疗的总有效率为35.7%。2R/2R和2R/3R基因型组(27例)化疗的有效率为55.6%(15/27),明显高于3R/3R基因型组(29例)的17.2%(5/29)(P<0.01)。2R/2R和2R/3R基因型组II度以上毒副反应的发生率略高于3R/3R基因型组。结论TS基因5′-UTR多态性与晚期胃癌对5-FU为基础的化疗敏感性相关。5′-UTR基因型检测有助于指导晚期胃癌的化疗。Objective To investigate the relationship between polymorphism in the 5＇-UTR of thymidylate synthase gene （TS） and sensitivity of stomach cancer （SC） to fluoropymidine （5-FU） - based chemotherapy. Methods A total of 56 cases with advanced SC were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. TS 5＇-UTR genotypes were detected by PCR method. The objective responses and toxicities were evaluated according to RECIST criteria. Results Of all the cases, the frequencies of 5＇-UTR 2R/2R, 2R/3R and 3R/3R genotypes were 5.4%, 42. 8% and 51.8%, respectively. The overall response rate to 5-FU- based chemotherapy was 35.7%. The response rate to therapy in patients with TS 2R/2R and 2R/3R genotypes was significantly higher than that in patients with 3R/3R genotype（55.6% vs. 17.2%） （P〈0. 01）. The incidence rates of the treatment-related more than Ⅱ grade side effect with the 2R/2R and 2R/3R genotype were slightly higher than that of the 3R/3R genotypes. Conclusion The polymorphism of TS 5＇-UTR is associated with clinical response to 5-FU-based chemotherapy, suggesting that TS 5＇-UTR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.

关 键 词：胃癌 胸苷酸合成酶 化学治疗 多态性 

分 类 号：R735[医药卫生—肿瘤]