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

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

目的 探讨中国人中存在的错配修复基因 h ML H1Val384Asp在大肠癌、胃癌、食道癌发病中的作用。方法 中国汉族人 10 1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、10 0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 h ML H1基因的第 12外显子 ,比较分析 Val384Asp的检出率。结果 6 %的正常人携带 h ML H1基因Val384Asp;小于 45岁的大肠癌患者中 h ML H1基因 Val384Asp的检出率高于正常对照 (P<0 .0 5 ) ;显著性差异还存在于具有癌症家族史的胃癌患者及其亲属与正常对照的比较 (P<0 .0 5和 P<0 .0 1) ;食道癌患者及其亲属与正常对照之间的比较无显著差异 (P>0 .0 5 )。结论 中国汉族人中 h ML H1基因Val384Asp等位基因频率约 3% ,这一错义突变可能在中国人部分大肠癌、胃癌的发病中起作用。

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.