亚甲基四氢叶酸还原酶基因多态性与乳腺癌化疗敏感性的关系

目的观察叶酸代谢的关键酶亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态与乳腺癌患者对化疗敏感性的关系。方法收集经病理学确诊的晚期乳腺癌患者61例,所有病例化疗前抽静脉血,提取白细胞DNA,用PCR-RFLP技术检测MTHFR基因型。接受6种不同的化疗方案化疗。结果61例乳腺癌癌患者中,MTHFR C/C基因型17例(27.9%)、C/T 29例(47.5%)、T/T 15例(24.6%)。MTHFR A1298C A/A基因型42例(68.9%),17例(27.9%)A/C基因型,2例(3.3%)C/C基因型。化疗总有效率为67.2%(41/61),其中CR3例(4.9%),PR38例(62.3%),SD15例(24.6%),PD5例(8.2%)。6种化疗方案的有效率无统计学差异(P=0.397)。MTHFR C/C基因型、C/T基因型、T/T基因型的有效率分别为58.8%、58.6%、93.3%,T/T基因型患者的有效率显著高于C/C基因型(P=0.041)和C/T基因型患者(P=0.034)。MTHFR A1298C A/A基因型、A/C基因型、C/C基因型的有效率分别为71.4%、64.7%、0.0%,MTHFR A1298C A/A基因型患者的有效率与A/C基因型(P=0.756)、C/C基因型患者之间无统计学差异(P=0.096)。结论本研究初步结果显示MTHFR C677T基因多态性对预测乳腺癌化疗疗效具有较好的临床应用价值。

METHYLENE TETRAHYDROFOLATE REDUCTASE POLYMORPHISM ON CHEMOSENSITIVITY OF ADVANCED BREAST CANCER

Objective: Methylene tetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of folic acid and plays an important role in the methylation of DNA.The activity of MTHFR can influence the methylation of DNA.Our research observed the relationship between chemosensitivity of advanced breast cancer and polymorphism of MTHFR.Methods We collected 61 specimens from advanced breast cancer patients with final diagnosis of pathology.The genotypes of MTHFR were detected by PCR-RFLP methods.These patients were treated with six different chemotherapy regimens.Results There is no significant difference among the response rate of the six different chemotherapy regimens(P>0.05).The response rate of chemotherapy on MTHFR T/T genotype is much higher than that of MTHFR C/C genotype(P=0.041) and MTHFR C/T genotype,A1298C A/C genotype(P>0.05) and A1298C C/C genotype(P=0.096).Conclusion Polymorphism of MTHFR can influence the chemosensitivity of advanced breast cancer and is of value as the guideline of breast cancer therapy.