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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
Objective To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C polymorphism and 5-FU-based chemosensitivity and toxicity in gastric cancer patients. Methods Seventy - five patients with pathologically diagnosed advanced gastric cancer were recruited. Venous blood was collected before chemotherapy and white blood cell DNA was extracted. MTHFR genotypes were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR - RFLP). All patients were treated with 5-FU-based chemotherapy. Results Among the 75 patients with advanced gastric cancer, the frequencies of MTHFR C677TC / C, C / T and T / T genotypes were 24 (32.0%), 33 (44.0%) and 18 (24.0% 52 cases (69.3%), 22 cases (29.3%) and 1 case (1.3%) were MTHFR A1298CA / A, A / C and C / C genotypes, respectively. %. (2) The effective rate of chemotherapy for MTHFR C677T T / T genotype was 83.3%, significantly higher than that of T / C genotype (15.2%, x2 = 22.27, P = 0.000) and C / C genotype %, X2 = 23.44, P = 0.000). The chemosensitivity of patients with the C677T T / T genotype was 7.64 times greater than those with the C677T C allele (adjusted for gender, age, previous history of adjuvant chemotherapy and chemotherapy, 95% CI: 3.14-18.62). MTHFR A1298C A / A genotype was significantly higher (36.5%) than those with the A1298C C (13.0%) allele (x2 = 419, P = 0.041; adjusted OR = 3 75, 95% CI: 0.94-14.87). The effective rate of chemotherapy (86.7%) with MTHFR C677T T / T genotype and A1298C A / A genotype was significantly higher than that of other genotypes (Fisher’s exact: P = 0.000, adjusted OR = 6.57.95