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目的:观察亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态和胸苷酸合成酶(TS)基因5′-UTR(28bp)、3′-UTR(6bp)多态与乳腺癌患者对化疗敏感性的关系。方法:乳腺癌患者87例,其中新辅助化疗61例,晚期姑息化疗26例。分别接受CAF、AT方案化疗。所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测分析MTHFR和TS基因型。结果:87例乳腺癌患者化疗总有效率为69.0%。39例接受CAF方案化疗患者有效率为61.5%,48例接受AT方案化疗患者的有效率为75.0%。MTHFRC677TT/T基因型患者的化疗有效率(87.5%)显著高于C/C基因型患者(52.4%),χ2=6.24,P=0.01。CAF方案化疗组患者中,MTHFRC677TT/T、T/C基因型患者的化疗有效率(90.0%、68.8%)显著高于C/C基因型患者(30.8%),χ2=8.74,P=0.011。61例新辅助化疗患者,MTHFRC677TT/T基因型患者的化疗病理反应率(83.3%)显著高于C/C基因患者(35.7%),χ2=7.619,P=0.006。TS6bp-6/-6基因型患者的化疗病理反应率(80.8%)显著高于-6/+6基因患者(46.7%),χ2=6.911,P=0.009。接受AT方案化疗的患者中TS-6/-6基因型患者的化疗病理反应率(92.9%)显著高于-6/+6基因型患者(45.5%),χ2=6.866,P=0.009。结论:MTH-FRC677T和TS6bp基因多态性对指导乳腺癌临床个体化治疗具有较高的应用价值。
OBJECTIVE: To observe the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C polymorphisms and the 5’-UTR (28bp), 3’-UTR (6bp) polymorphisms of the thymidylate synthase (TS) Patient’s sensitivity to chemotherapy. Methods: 87 cases of breast cancer patients, including neoadjuvant chemotherapy in 61 cases, late palliative chemotherapy in 26 cases. Respectively receive CAF, AT regimen chemotherapy. Venous blood was drawn before chemotherapy, leukocyte DNA was extracted, and MTHFR and TS genotypes were detected by PCR-RFLP. Results: The total effective rate of chemotherapy in 87 patients with breast cancer was 69.0%. The response rate of 39 patients receiving CAF regimen was 61.5%, and that of 48 patients receiving AT regimen was 75.0%. The effective rate of chemotherapy (87.5%) in MTHFRC677TT / T genotype patients was significantly higher than that in C / C genotypes (52.4%), χ2 = 6.24, P = 0.01. Among patients with CAF regimen chemotherapy, the effective rates of chemotherapy (90.0%, 68.8%) in patients with MTHFRC677TT / T and T / C genotypes were significantly higher than those in C / C genotypes (χ2 = 8.74, P = 0.011). In 61 patients with neoadjuvant chemotherapy, the pathological response rate (83.3%) in MTHFRC677TT / T genotype was significantly higher than that in C / C gene (35.7%), χ2 = 7.619, P = 0.006. The pathological response rate (80.8%) of TS6bp-6 / -6 genotype was significantly higher than that of -6 / + 6 (46.7%), χ2 = 6.911, P = 0.009. The chemotherapy response rate (92.9%) in patients with TS-6 / -6 genotype was significantly higher than that in the -6 / + 6 genotype (45.5%), χ2 = 6.866, P = 0.009. Conclusion: The polymorphisms of MTH-FRC677T and TS6bp are of high value in clinical individualized therapy of breast cancer.