错配修复基因hMLH1错义突变Val384Asp与四种肿瘤遗传易感性的研究

Study on the relationship between genetic polymorphism Va1384Asp in hMLH1 gene and the risk of four different carcinomas

目的 了解中国人hMLH1基因Va1384Asp错义突变在四种肿瘤中的存在状况。方法在中国汉族人群中分别提取233例大肠癌患者、273例胃癌患者、111例乳腺癌患者、90例食管癌患者和268名健康人外周血细胞的基因组DNA;采用聚合酶链反应扩增hMLH1基因第12外显子的部分DNA片段(217bp),变性高效相色谱检测,DNA测序验证,比较分析Val384Asp基因型在四种肿瘤中的分布。结果 6.34％正常人群携带Val384Asp,在大肠癌患者和胃癌患者中Val384Asp的检出率与正常人群相比差异有统计学意义(P<0.05),尤其在<45岁的大肠癌患者和<50岁的胃癌患者中,Val384Asp的检出率与正常人群相比差异有统计学意义(P<0.01),而在乳腺癌患者和食管癌患者中Val384Asp的检出率与正常人的相同或相近。结论 Val384Asp错义突变作为中国人hMLH1基因上的一个多态位点,是大肠癌和胃癌遗传易感因素,可作为中国人胃肠道肿瘤,尤其是低龄胃肠道肿瘤高危人群筛选的候选指标。

Objective To investigate the association of genetic polymorphism Va1384Asp in hMLH1 gene with the risk of colorectal, gastric, esophageal and breast carcinomas. Methods A case-control study was taken to investigate the role of Va1384Asp in hMLH1 gene in developing these four carcinomas. 233 colorectal, 273 gastric, 90 esophageal and 111 breast cancer patients were included, as well as 268 heathy individual served as controls. Peripheral white blood cell DNA was obtained from all subjects, hMLH1 gene Va1384Asp was analysed using a PCR-based DHPLC while the existence of Va1384Asp were verified by DNA sequencing. Results 6.34% of the heathy individuals were identified as Va1384Asp carriers and significant differences existing between colorectal cancer patients or gastreic cancer patients and controls, especially between younge aged patients and controls. Conclusion Determination of Va1384Asp in hMLH1 gene single nucleotide polymorphism seemed to be suitable for identifying individuals with increased risk of gastrointestinal cancer in the Chinese population.