胸苷酸合成酶基因多态性与氟尿嘧啶治疗晚期胃癌疗效相关性的研究

目的：研究胸营酸合成酶（TS）基因的5’-UTR28bp核苷酸片段重复多态和3’-UTR1494修饰处存在的6bp核苷酸片段缺失或插入多态与应用以氟尿嘧啶（5-FU）为主的联合化疗方案治疗胃癌疗效的相关性。方法：收集经病理学确诊的晚期胃癌74例，所有患者使用以5-Fu为主的化疗方案治疗，化疗前抽静脉血，提取白细胞DNA用PCR—DHPLC技术检测TS5’-UTR1R28bp及3’-UTR6bp基因型：结果：（1）74例胃癌患者的TS5’-UTR28bp31t／3R、2R／2R＋21t／3R基因型分别为21．6％（16／74）和78．4％（58／74），而相应的化疗客观有效率分别为6．3％（1／16）和36．2％（21／58），3R／3R组的化疗疗效比2R／2R＋2R／31／绀低（X^2=4．05，P〈0．05）；（2）74例胃癌患者的TS3’-UTR＋／＋6bp、＋／-6bp、-／-6bp基因型分别为5．4％（4／74）、52．7％（39／74）和41．9％（31／74），相应各组的化疗有效率分别为0（0／4）、25．6％（10／39）和41．9％（13／31），不同基因型与化疗疗效之间无相天性（P=0．076）。结论：TS5’-UTR28bp多态性与5-FU疗效之间存在相关性，其检测有助于指导晚期胃癌选择5-FU化疗，而TS3’-UTR多态性与5-FU疗效之间没有显示相关性，

The investigation of relationship between the polymorphism of thymidylates synthease gene and therapeutic effect of stomach cancer to fluorouracil-based chemotherapy

Objective：To investigate the relationship between polymorphism of thymidylates synthease gene in the 5 ＇ -untrans- lated region（5＇-UTR） and 3 ＇-untranslated region （3＇-UTR） and therapeutic effect of stomach cancer （SC）to fluorouracil-based chemotherapy. TS gene promoter have either doubler or triple tandem repeats of a 28bp sequence in 5 ＇ -UTR and a 6bp variation at bp1494 in 3＇ -UTR. Methods：Seventy-four advanced SC patients were analyzed, which were diagnosed by pathology. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before chemotherapy. TS 5＇ -UTR and 3＇ UTR genotypes were detected by PCR-DHPLC method. Results：Of all the 74 cases,the proportion of 3R/3R genotype and 2R/2R, 2R/3R genotypes were 21.6% （16/74） and 78.4% （58/74）. The response rates to chemotherapy were 6. 3% （1/16） and 36. 2% （21/58）. The latter was significantly higher than the former, （X2 = 4. 05, P 〈 0. 05）. Of all the 74 cases, the proportion of TS 5＇ UTR ＋ / ＋ 6bp, ＋/-6bp and-/-6bp were 5.4% （ 4/74 ） , 52. 7 % （39/74） and 41.9% （ 31/74）. The response rates to chemotherapy were 0（0/4） ,25.6% （ 10/39 ） and 41.9% （ 13/31 ）. There was no significant difference in these groups（ P = 0. 076）. Conclusion： The study suggested that the polymorphism of TS 5＇-UTR was associated with therapeutic effect of SC to 5-FU. However,there was no relationship between the polymorphism of TS 3＇ -UTR and the therapeutic effect of 5-FU. It was suggested that detection of TS 5＇ -UTR genotype could guide the chemotherapy of the advanced SC.