胸苷酸合成酶基因多态对接受氟尿嘧啶辅助化疗胃癌患者预后的影响

The influence of thymidylate synthase polymorphisms on the prognosis of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy

目的:研究胸苷酸合成酶(thymidylate synthase,TS)基因增强子区(enhancer region,ER)串联重复序列多态和3’端非翻译区(untranslated region,UTR)6bp缺失或插入多态(del6/ins6)对接受以氟尿嘧啶(fluorouracil,FU)为基础的辅助化疗胃癌患者预后的影响。方法:116例经确诊的胃癌患者,采用以FU为基础的方案进行辅助化疗。应用PCR技术检测TS基因多态。结果:在116例胃癌患者中,TSER 2R/2R、2R/3R和3R/3R基因型频率分别为7.8%(9/116)、31.9%(37/116)和60.3%(70/116);TS ins6/ins6、ins6/del6和del6/del6基因型频率分别为9.5%(11/116)、41.4%(48/116)和49.1%(57/116)。携带ins6/ins6基因型患者的总生存期显著短于携带del6/del6(P=0.017)或ins6/del6基因型患者的生存期(P=0.022),不同TSER基因型胃癌患者的中位无复发生存期差异无统计学意义(P>0.05)。COX多因素分析结果显示,ins6/ins6基因型患者的死亡风险增加。结论:TS 3’-UTR ins6/del6基因多态性是接受以FU为基础的辅助化疗胃癌患者的独立预后因素。

Objective： To investigate the effects of the tandem repeat polymorphisms in the enhancer region （ER） of thymidylate synthase （TS） gene and the 6-bp deletion/insertion （de16/ins6） polymorphism in the 3＇ untranslated region （3＇ -UTR） of TS gene on the clinical outcomes of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy. Methods ： One hundred and sixteen patients with gastric cancer were treated with 5-FU-based adjuvant chemotherapy. The polymorphisms of TSER and TS 3＇ -UTR in those patients were determined by polymerase chain reaction （PCR） method. Results： Of the 116 patients, the frequencies of the TSER 2R/ 2R, 2R/3R and 3R/3R were 7.8% （9/116） , 31.9% （37/116） , and 60.3% （70/116） , respectively; the frequencies of the TS 3＇ UTR ins6/ins6, ins6/de16 and del6/de16 were 9.5% （11/116） , 41.4% （48/116） and 49.1% （57/116） , respectively. The median survival period in ins6/ins6 carriers was significantly shorter than that of del6/de16 （ P = 0.017 ） or ins6/de16 （ P = 0.022 ） carriers. There was no significant difference in median relapse-free survival period between different TSER carriers （ P 〉 0.05 ）. COX multivariate analysis showed that the ins6/ins6 carriers had increased death risk （ P 〈 0.05 ） compared to the other two genotypes. The median no-recurrence survival period had no statistical difference between them. Conclusion： The polymorphism of TS 3 UTR ins6/de16 may he an independent factor for the prognosis of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy.