肺癌患者O^6-甲基鸟嘌呤DNA甲基转移酶基因多态性研究

Single-nucleotide polymorphisms of human O^6-methylguanine-DNA methyltransferase(MGMT)gene in lung cancer patients from south China

目的 检测人类O6 甲基鸟嘌呤 DNA甲基转移酶 (MGMT)基因 5个外显子的单核苷酸多态 (SNPs)及其与肺癌的关系。方法 采用聚合酶链式反应 (PCR) 单链构像多态性 (SSCP) DNA直接测序法对 10 0例正常人和 6 0例肺癌患者外周血白细胞进行MGMT基因SNPs研究。结果 在正常人群和肺癌患者中检测到MGMT基因的第 3、4外显子上存在着SNPs ,即第 3外显子上第 2 5 0位碱基C被T所取代 ,导致错义突变 (CTTTTT ,使Leu84Phe) ;第 4外显子上第 2 80位碱基C被T取代 ,导致同义突变 (TTCTTT ,均编码Phe)。这两个位点的SNPs在两组人群间的检出率差异无显著性(P >0 0 5 )。结论 MGMT基因第 3、4外显子上存在着SNPs ,其多态改变与肺癌形成的关系较弱。

Objective To investigate single-nucleotide polymorphisms (SNP s)of exons 1～5in human O 6-methylguanine-DNA methyltransferase(MGMT)gene and their relationship to the susceptibility to lung cancer.Methods The Polymorphisms of MGMT gene exons 1～5were analyzed with PCR-SSCP-DNA sequencing in 160 chinese Han people (100 healthy people and 60 lung cancer patients).Results A polymorphism of exon 3,a C-to-T missensemutation was detected at the first base of codon 84(TTCTTT,Leu84Phe);and a polymorphism of exon 4,a C-to-T same mutation,was detected at the third base of codon 94(TTCTTT,both encode Phe),For the polymorphisms of the two sites,there was no statistical significance between the two groups (P>0.05).Conclusion There were polymorphisms of exon 3 and 4 in MGMT gene,while the relationship between the polymorphisms and the occurrence of lung cancer might be weak.