中国人、日本人和德国人中hMLH1基因Val 384Asp的检测及在大肠癌发病中的作用  

Val384Asp IN hMLH1 GENE IN CHINESE, JAPANESE AND GERMAN AND ITS ETIOLOGICAL ROLE IN COLORECTAL CANCER

作　　者：王亚平[1,2] 李金田[1,2] 李忠佑 王建东[1,2] 

机构地区：[1]江苏省肿瘤防治研究所 [2]德国波恩大学人类遗传学研究所

出　　处：《中华医学遗传学杂志》1998年第5期263-266,共4页Chinese Journal of Medical Genetics

基　　金：国家留学基金

摘　　要：目的探讨ｈＭＬＨ１基因Ｖａｌ３８４Ａｓｐ错义突变在中国人、日本人和德国人中的存在频率及其在大肠癌发病中的可能作用。方法应用ＰＣＲ－ＳＳＣＰ和ＤＮＡ序列分析技术检测２６例中国汉族人大肠癌患者、８０例健康中国汉族人、８０例健康日本人、１０９例德国人大肠癌患者和１００例健康德国人的正常体细胞ＤＮＡ，分析ｈＭＬＨ１基因的第１２外显子。结果４／２６中国人大肠癌患者（其中发病年龄小于５０岁的患者３／９）、３／８０健康中国人、４／８０健康日本人携带ｈＭＬＨ１基因Ｖａｌ３８４Ａｓｐ（杂合型），而德国人大肠癌患者和健康人群中均未检出这一突变。比较表明，发病年龄小于５０岁的中国人大肠癌患者中ｈＭＬＨ１基因Ｖａｌ３８４Ａｓｐ检出率高于中国健康人群（Ｐ＝０．０１３）、中国人和日本人中的检出率高于德国人。结论Ｖａ１３８４Ａｓｐ是中国人、日本人ｈＭＬＨ１基因上的一个多态位点，可能在部分大肠癌的发病中起到作用，并可能影响突变基因携带者大肠癌的发病年龄。Objective To investigate Val384Asp of hMLH1 gene in Chinese, Japanese and German after the missense mutation were identified in Chinese colorectal cancer patients and to inquire into the etiological role of this mutation in colorectal cancer.Methods Genomic DNA extracted from normal colon tissue or peripheral blood 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 26 Chinese and 109 German colorectal cancer patients and in 80 healthy Chinese, 80 Japanese and 100 German individuals.Results Val384Asp in hMLH1 gene was found in 4 out of 26 Chinese colorectal patients; 3 of them were out of the 9 patients with colorectal cancer at young age (<50 years). Although 3 and 4 carriers of Val384Asp in hMLH1 gene were identified in 80 healthy Chinese and 80 healthy Japanese individuals respectively, none were identified in German neither in 109 colorectal cancer patients, nor in 100 healthy German individuals. The frequency of Val384Asp in hMLH1 gene in the Chinese with colorectal cancer at young age was higher than that in Chinese healthy individuals ( P =0.013).Conclusion Val384Asp can be taken as a polymorphism in hMLH1 gene in Chinese and Japanese populations and may have a potential effect on age at onset of colorectal cancer.

关 键 词：大肠肿瘤 HMLH1基因 错义突变 中国人 日本人 

分 类 号：R735.340.4[医药卫生—肿瘤]