hMLH1-93G/A基因多态性与结直肠癌的相关性研究

摘要

hMLH1是DNA错配修复(MMR)系统的重要成员,在DNA复制过程中识别和修复错配碱基,其基因多态性对散发性结直肠癌(CRC)的诊断有重要价值.目的:探讨hMLH1启动子区-93G/A基因多态性与CRC的关系.方法:连续收集2008年1月-2010年10月的CRC患者312例,纳入同期正常对照300例.抽提所有入选者外周血白细胞DNA,以TaqMan MGB探针荧光定量PCR检测hMLH1启动子区-93G/A基因多态性.结果:CRC组患者hMLH1-93G/A各基因型频率与正常对照组相比.差异无统计学意义(P=0.219).对CRC组行分层分析示Dukes C/D期患者的A等位基因和AA基因型频率明显高于MB期患者(60.5%对48.1%,/a=0.004;39.8%对23.3%,P=0.015),淋巴结转移者的A等位基因和AA基因型频率亦明显高于无淋巴结转移者(60.5%对49.1%,P=0.010;39.5%对25.0%,P=0.031).结论:hMLH1启动子-93G/A基因多态性与CRC的发生无关.但A等位基因和AA基因型可能与CRC的进展有关.%Background: hMLH1 is an essential member of DNA mismatch repair (MMR) system, which plays an important role in the recognition and repairment of mismatched bases in DNA replication. hMLH1 gene polymorphism is of significant value in the diagnosis of sporadic colorectal cancer (CRC). Aims: To assess the correlation between hMLH1-93G/A promoter gene polymorphism and CRC. Methods: Three hundred and twelve CRC patients and 300 controls from Jan. 2008 to Oct.2010 were enrolled in this study. DNA was extracted from the peripheral white blood cells and hMLH1-93G/A promoter gene polymorphism was detected by TaqMan MGB probe fluorescent quantitative PCR. Results: The frequencies of hMLH1-93G/A genotype were not significantly different between CRC patients and controls (P=0.219). Stratified analysis of CRC patients showed that the frequencies of A allele and AA genotype in patients with Dukes C/D stage and lymphatic metastasis were significantly higher than those in patients with Dukes A/B stage (60.5％ vs. 48.1％, P=0.004; 39.8％ vs.23.3％, P=0.015) and without lymphatic metastasis (60.5％ vs. 49.1％, P=0.010; 39.5％ vs. 25.0％, P=0.031). Conclusions:hMLH1-93G/A promoter gene polymorphism has no correlation with the development of CRC, but its A allele and AA genotype are related to the progression of CRC.