亚甲基四氢叶酸还原酶基因多态性与胃癌化疗的敏感性关系的研究

目的 研究亚甲基四氢叶酸还原酶(MTHFR) 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 收集经病理学确诊的晚期胃癌患者75例,病例化疗前均抽静脉血,提取白细胞DNA,用聚合酶链反应-限定性片段长度多态性技术检测MTHFR基因型。所有患者经5-FU为基础的化疗方案治疗。结果 (1)在75例晚期胃癌患者中,MTHFR C677TC／C、C／T、T／T基因型者分别为24例(32.0％)、33例(44.0％)和18例(24.0％);MTHFR A1298CA／A、A／C、C／C基因型者分别为52例(69.3％)、22例(29.3％)和1例(1.3％);经化疗后22例患者有效,总有效率29.3％。(2)MTHFR C677T T／T基因型者化疗的有效率为83.3％,显著高于T／C基因型者(15.2％,x2=22.27,P=0.000)和C／C基因型者(8 3％,x2=23.44,P=0.000)。C677T T／T基因型患者化疗敏感性是携带C677T C等位基因者的7.64倍(调整了性别、年龄、以往辅助化疗史及化疗方案,95％CI:3.14-18.62)。MTHFR A1298C A／A基因型者的有效率(36.5％),显著高于携带A1298C C(13.0％)等位基因者(x2=4 19,P=0.041;调整OR=3 75,95％CI:0.94-14.87)。同时携带MTHFR C677T T／T基因型和A1298C A／A基因型者化疗的有效率(86.7％)显著高于其他基因型者(15.0％,Fisher's exact:P=0.000,调整OR=6.57.95

Polymorphism of methylenetetrahydrofolate reductase and sensitivity of stomach cancer to fluoropyrimidinebased chemotherapy

Objective To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy m advanced stomach cancer (SC). Methods 75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method Results (1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0% , 44.0% and 24.0% , while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3% , 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83. 3% ) was significantly higher than the C677T C/T genotype (15. 2 % , x2 = 22 27, P = 0.000) or the C677T C/C genotype (8. 3 % , x2 = 23. 44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95 % CI: 3. 14- 18.62 ). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0% ,x2 = 4.19,P= 0.041,adjusted OR = 3.75 ,95% CI :0. 94-14. 87) The response rate to therapyamong patients with MTHFR C677T T/T and A1298C A/A genotypes (86 7% ) was significantly higher than other groups of C677T and A1298C genotypes (15.0% , Fisher exact: P = 0.000, adjusted OR = 6 57,95%CI:2.8-15 6) (3) The mcidence rates of nausea/vomiting m MTHFR C677T T/T, C/T or A1298C A/A genotypes were sigmficantly higher than other genotypes, but the mcidence rates of other treatmentrelated adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different. Conclusion These results m the present study suggested that the polymorphisms of MTHFR were associated with clmical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.