论文部分内容阅读
目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态与胃癌患者对5-FU为基础的化疗敏感性和毒性的关系。方法:晚期胃癌患者106例,用聚合酶链反应-限定性片段长度多态性(PCR-RFLP)技术检测白细胞DNAMTH-FR基因型。所有患者经5-FU为基础的化疗方案治疗。结果:1)在106例晚期胃癌患者中,MTHFRC677TCC、CT、TT基因型分别占31·1%、46·2%和22·6%;MTH-FRA1298CAA、AC、CC基因型者分别为69·8%、29·2%和0·9%;化疗总有效率35·8%。2)MTHFRC677TTT基因型携带者化疗有效率(83·3%)明显高于C677TCT(24·5%;P=0·000)和C677TCC(18·2%;P=0·000)。而MTHFRA1298CAA组有效率(43·2%)亦明显高于A1298CAC+CC组(18·8%,P=0·009)。3)在CFL、CFH、LFP方案治疗的患者中,C677T变异子携带者对化疗敏感性更高。对A1298C多态性,患者接受CFL方案化疗时,1298AA纯合子携带者有效率高于1298CT/CC患者。4)MTHFRC677TTT、CT或A1298CAA多态性携带者化疗相关的恶心/呕吐发生率明显高于其他三种多态性者。结论:MTHFR基因多态性的检测可能是晚期胃癌患者接受5-FU为基础化疗疗效和毒副反应的良好预测指标。
Objective: To investigate the relationship between MTHFR gene C677T and A1298C polymorphisms and 5-FU-based chemotherapy sensitivity and toxicity in patients with gastric cancer. Methods: One hundred and sixty patients with advanced gastric cancer were detected by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique to detect leukocyte DNAMTH-FR genotype. All patients were treated with a 5-FU-based chemotherapy regimen. Results: 1) In 106 patients with advanced gastric cancer, the MTHFRC 677 TCC, CT, TT genotypes accounted for 31.1%, 46. 2%, and 22.6%, respectively; the MTH-FRA1298CAA, AC, and CC genotypes were 69. 8%, 29.2%, and 0.9%; total chemotherapy efficiency 35.8%. 2) The efficiency of chemotherapy with MTHFRC677TTT genotype carrier (83. 3%) was significantly higher than that of C677TCT (24.5%; P=0.000) and C677TCC (18. 2%; P=0.000). The MTHFRA1298CAA group’s efficiency (43·2%) was also significantly higher than that of the A1298CAC+CC group (18.8%, P=0.009). 3) In patients treated with the CFL, CFH, and LFP regimens, the C677T variant carriers are more sensitive to chemotherapy. For the A1298C polymorphism, 1298AA homozygous carriers were more effective than 1298CT/CC patients when receiving CFL regimen chemotherapy. 4) The incidence of chemotherapy-related nausea/vomiting in MTHFRC677TTT, CT, or A1298CAA polymorphism carriers was significantly higher than in the other three polymorphisms. Conclusion: The detection of MTHFR gene polymorphism may be a good predictor for the efficacy and toxicity of 5-FU-based chemotherapy in patients with advanced gastric cancer.