胸苷酸合成酶基因多态性预测氟尿嘧啶在晚期食管癌中的化疗疗效

Prognostic value of the TS genetic polymorphisms and therapeutic effect in advanced esophageal cancer treated with fluorouracil-based chemotherapy

目的研究胸苷酸合成酶(TS)和亚甲酰四氢叶酸还原酶(MTHFR)基因多态性与应用以氟尿嘧啶为基础的化疗方案治疗晚期食管癌疗效的相关性。方法收集经病理学确诊的晚期食管癌患者107例,并应用顺铂联合氟尿嘧啶三周方案化疗,最终98例患者按要求完成该研究。检测患者上述基因位点的多态性,分析基因多态性与反应率(response rate,RR)和无进展生存时间(progression free survival,PFS)的关系。结果TS-5′UTR端为2R2R或2R3C或3C3C型患者反应率和无进展生存时间优于2R3G或3C3G或3G3G(P=0.007和0.018),其他位点基因多态性与反应率和无进展生存时间无显著相关性。结论TS-5'UTR位点为2R2R或2R3C或3C3C型的晚期食管癌患者与氟尿嘧啶疗效存在相关性,有助于指导晚期食管癌选择氟尿嘧啶化疗。

Aim To investigate the relationship between genetic polymorphisms of TS and MTHFR and the therapeutic effect of fluorouracil-based chemotherapy on advanced esophageal cancer.Methods 107 patients with advanced esophageal cancer were enrolled in this study,which were diagnosed by pathology,98 of which were eligible for analysis.All patients received cisplatin /fluorouracil chemotherapy repeated every three weeks.Genetic polymorphisms examined herein included those in the genes coding TS and MTHFR.Then we analyzed the relationships between genetic polymorphisms and clinical outcome.Results 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 and 0.018）.There were no significant relationships between response rate and PFS and other genetic polymorphisms.Conclusion The advanced esophageal cancer patients with 2R2R or 2R3C or 3C3C genotype in TS-5＇UTR were more sensitive to fluorouracil-based chemotherapy,which could guide the chemotherapy of the advanced esophageal cancer.