中国人消化道肿瘤发病的遗传背景因素——错配修复基因hMLH1错义突变Va1384Asp

目的 探讨中国人中存在的错配修复基因ｈＭＬＨ１ Ｖａ１３８４Ａｓｐ在大肠癌，胃癌，食道癌发病中的作用。方法 中国汉族人１０１例大肠癌患者，７９例胃癌患者，７６例食道癌患者，７９例和７６例胃癌和食道癌患者的亲属，１００名正常对照，各取正常体细胞，提取基因组ＤＮＡ。ＰＣＲ－ＳＳＣＰ和ＤＮＡ序列分析技术检测ｈＭＬＨ１基因的第１２外显子，比较分析Ｖａｌ３８４Ａｓｐ的检出率。

One of the etiological factors of digestive tract cancers in Chinese: the missense mutation Val384Asp in the hMLH1 gene

Objective To investigate the etiological role of Val384Asp in the hMLH1 gene, which may be a polymorphism in Chinese, in colorectal,gastric and esophageal cancers. Methods Genomic DNA extracted from normal tissues were subjected to analysis in exon 12 of the hMLH1 gene by single strand conformation polymorphism(SSCP) followed by DNA sequencing of aberrant bands in 101 colorectal, 79 gastric and 76 esophageal cancer patients; in 79 and 76 first degree relatives of gastric cancer and esophageal cancer patients respectively; and in 100 healthy control individuals. Results Six percent of Chinese healthy individuals were the carriers of Val384Asp in the hMLH1 gene. There were significant differences in the frequencies of Val384Asp in the hMLH1 gene between the patients with colorectal cancer at young age(<45 years) and the control individuals ( P <0.05), and between the gastric cancer patients with family history, the first degree relatives and the control group ( P <0.05 and P<0.01 respectively). No difference was found between the esophageal cancer patients, their relatives and healthy controls.Conclusion The alleles frequency of Val384Asp in the hMLH1 gene in Chinese is three percent. This missense mutation may play a part in the etiology of colorectal and gastric cancers in Chinese.