ERCC1和TS基因多态性在预测顺铂联合5-氟尿嘧啶治疗晚期食管癌疗效中的意义

Prognostic value of the ERCC1 and TS genetic polymorphisms in advanced esophageal cancer treated with cisplatin/fluorouracil chemotherapy

目的:探讨切除修复交叉互补基因1(excision repair cross-complementation group1,ERCC1)、胸苷酸合成酶(thymidylate synthase,TS)、谷胱苷肽-S-转移酶P1(glutathione-S-transferase P1,GSTP1)和亚甲酰四氢叶酸还原酶(methylenetetrahydrofo-late reductase,MTHFR)的基因多态性,在预测顺铂联合5-氟尿嘧啶治疗晚期食管癌疗效中的作用。方法:107例晚期食管癌患者入组并行顺铂联合5-氟尿嘧啶共3个周期的化疗,最终98例患者按要求完成该治疗且有随访资料。通过测序的方法检测98例患者上述基因位点的多态性,分析基因多态性与化疗客观反应率(response rate,RR)和无进展生存(progression-freesurvival,PFS)期的关系。结果:ERCC1-C8092A位点A/A或A/C型患者的RR和PFS期优于C/C型患者(P=0.010和P=0.008)。TS基因5’端非翻译区(five prime untranslated region,UTR)为2R2R、2R3C或3C3C型患者的RR和PFS期优于2R3G、3C3G或3G3G型患者(P=0.007和P=0.018)。GSTP1和MTHFR基因位点的多态性与RR和PFS期无显著相关性。结论:ERCC1-C8092A位点为A/A或A/C型,TS-5’UTR位点为2R2R、2R3C或3C3C型的晚期食管癌患者对顺铂联合5-氟尿嘧啶治疗方案更为敏感。

Objective：To investigate the values of genetic polymorphisms of excision repair cross-complementation group 1（ERCC1）,thymidylate synthase（TS）,glutathione-S-transferase P1（GSTP1） and methylenetetrahydrofolate reductase（MTHFR） in predicting the prognosis of advanced esophageal cancer patients treated with cisplatin/fluorouracil chemotherapy.Methods：One hundred and seven patients with advanced esophageal cancer were enrolled in this study,98 of which were eligible for analysis.All patients received cisplatin/fluorouracil chemotherapy repeated every three cycles.Genetic polymorphisms examined herein included those in the genes coding ERCC1,TS,GSTP1 and MTHFR.Then the relationships between genetic polymorphisms and response rate（RR） and progression free survival（PFS） time were analyzed.Results：The patients with A/A or A/C genotype in ERCC1-C8092A had a higher response rate and longer PFS than the patients with C/C genotype（P=0.010,P=0.008）;the patients with 2R2R or 2R3C or 3C3C genotype in TS-5＇UTR had a higher response rate and longer PFS than the patients with 2R3G or 3C3G or 3G3G（P=0.007,P=0.018）.There was no significant relationship between RR and PFS and other genetic polymorphisms.Conclusion：The advanced esophageal cancer patients with A/A or A/C genotype in ERCC1-C8092A and/or 2R2R or 2R3C or 3C3C genotype in TS-5＇UTR were more sensitive to cisplatin/fluorouracil chemotherapy.