应用DHPLC技术分析错配修复基因(hMLH1)T1151A多态与胃肠道肿瘤的遗传易感性

目的了解中国人hMLH1基因T1151A多态与胃肠道肿瘤的遗传易感性.方法采用病例对照研究设计,提取233例大肠癌(结,直肠癌)患者,273例胃癌患者和268例健康人外周血细胞的基因组DNA.PCR扩增hMLH1基因T1151A多态所在第12外显子的部分DNA片段(217 bp),变性高效液相色谱(DHPLC)检测,DNA测序验证,比较分析T1151A基因型在胃肠道肿瘤的分布.结果正常人群中T1151A多态T/A基因型频率为6.34%,其等位基因A频率为3.28%,在大肠癌患者和胃癌患者中T/A基因型频率与正常人群相比存在显著性差异,分别为11.6%(P=0.039)和12.1%(P=0.021),尤其在＜45岁的大肠癌患者和＜50岁的胃癌患者中,等位基因A频率与正常人群相比差异更为显著,分别为10.66%(P=0.002)和11.27%(P=0.001).结论T1151A作为中国人hMLH1基因上的一个多态位点,可能是中国人大肠癌和胃癌遗传易感因素,可作为中国人胃及大肠肿瘤、尤其是低龄胃及大肠肿瘤高危人群筛选的侯选指标.

Study on the association of genetic polymorphism Val384Asp in hMLH1 gene with the risk of gastrointestinal carcinoma

Objective To investigate the association of genetic polymorphism in hMLH1 gene T1151A with the risk of gastrointestinal cancer. Methods We conducted a case-control study to investigate whether such missense affect the risk of developing gastrointestinal cancer. Subjects included 233 colorectal cases, 273 gastreic and 268 heathy individual controls. Peripheral white blood cell DNA was obtained from all subjects. hMLH1 gene T1151A was analysed using a PCR-based DHPLC,the existence of T1151A were verified by DNA sequencing. Result About 6.34% heathy individuals were T1151A carries, the significant difference occurred between colorectal cancer patients and gastreic cancer patients vs. controls,especially between lower age patients and controls. Conclusion Determination of the hMLH1 gene T1151A single nucleotide polymorphism may be suitable to identify individuals with increased risk of gastrointestinal cancer in Chinese population.