肺癌患者MTHFR基因多态性与抑癌基因过甲基化的关系

目的：探讨亚甲基四氢叶酸还原酶基因多态性与肺癌易感性及抑癌基因甲基化的关系。方法：采用病例对照研究的方法，以限制性片段长度多态性方法，检测了93例肺癌患者及106例对照的MTHFR C677T基因型；用巢式甲基化特异性PCR（nMSP）法检测肺癌患者外周血血清中p16及MGMT基因的甲基化。结果：MTHFR C677T C/C,C/T,T/T基因型分布频率在病例组中分别为：29%、49.5%、21.5%，在对照组中分别为：36%、51%、19%，频率分布差异无统计学意义。病例组中p16甲基化检出率为68%（63/93），MGMT甲基化检出率为52%（48/93）。各基因型之间的p16与MGMT基因甲基化阳性率差异无统计学意义（ P >0.05）。结论：MTHFR基因 C677T多态性与肺癌发生之间未发现相关，MTHFR变异基因型（C/T,T/T）并非导致p16与MGMT基因甲基化的直接原因。

Relationship of Polymorphisms of MTHFR Gene and Hypermethylation of Tumor Suppressor Gene in Lung Cancers

Objective：To evaluate the possible association of the MTHFR gene C677T polymorphisms with the hypermethylation of p16 and MGMT gene in lung cancer. Methods：A retrospective case control study was designed in this investigation.The MTHFR genotypes of 93 cases and 106 controls were determined using a PCR-based restriction fragment length polymorphism(RFLP) method.The hypermethylation of p16 and MGMT gene in plasma of 93 cases of lung cancer by nested methylation specific polymerase chain reaction（nMSP）. Results：The frequencies of C/C,C/T,T/T genotypes of MTHFR gene C677T were 29%， 49.5% and 21.5% in cases and 36%，51% and 19% in controls,respectively.No significant difference of genotype distribution was found. Aberrant methylation of the p16 gene was detected in 63 from 93 cases(68%),and methylation of the MGMT gene was detected in 48 from 93 cases(52%).There was no significant difference among the different genotypes. Conclusion：No association between MTHFR gene C677T variant genotypes were and lung cancer was suggested. MTHFR C677T variant genotypes was not the direct reason of methylation of tumor suppressor gene.