错配修复基因hMLH1单核苷酸多态性T1151A在消化道肿瘤发病中的作用

在多次检出中国人大肠癌患者hMLH1基因T1151A的基础上，探讨这一单核苷酸多态性在不同人群中的存在状况及其在消化道肿瘤发病中的作用。方法：100例健康中国汉族人、80例健康日本人、100例健康德国人和109例德国人大肠癌患者、中国汉族人101例大肠癌患者、79例胃癌患者、76例食管癌患者及其胃癌和食管癌患者的亲属，取每例外周静脉血，提取基因组DNA；PCR-SSCP和DNA测序分析hMLH1基因的第12外显子。结果：hMLH1基因T1151A在中国和日本健康人群中的等位基因频率分别为3%和2.5%；与相应正常人群比较，<45岁的大肠癌患者中hMLH1基因T1151A的检出率较高(P<0.05)；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<0.05和P<0.01)；食管癌患者及其亲属与正常对照之间的比较无显著差异(P

The Etiological Role of the Single-nucleotide Polymorphism T1151A in the DNA Mismatch Repair Gene hMLH1 in Cancer of the G-I Tract.

To investigate the single-nucleotide polymorphism(SNP) T1151A in the hMLH1 gene in the Chinese, Japanese and German population; the same study was carried out in Chinese colorectal can-cer(CRC) patients; the etiological role of this SNP was explored in three cancers of the G-I tract. Methods: Genomic DNA was extracted from normal tissues and the specimens were subjected to analysis of the exon 12 of the hMLH1 gene by single strand conformation polymorphism(SSCP), followed by DNA sequencing of aberrant bands in 100 healthy Chinese, 80 healthy Japanese and 100 healthy German individuals, and in 101 Chinese and 109 German CRC patients, in 79 Chinese gastric and 76 Chinese eso-phageal cancer patients, as well as in 79 and 76 first degree relatives of gastric and esophageal cancer patients respectively. Results: The alleles frequency of T1151A in the hMLH1 gene in Chinese and Japanese healthy individuals are 3% and 2.5% respectively. There was significant difference in the frequency of T1151A in hMLH1 gene between the patients with CRC younger than 45 years and healthy individuals(P<0.05); and between gastric cancer patients with family history, their first degree relatives and heal-thy controls(P<0.05 and P<0.01 respectively). No significant difference was found between esophageal cancer patients, their relatives and healthy controls. This SNP has not been found in German healthy individuals nor in German CRC patients. Conclusions: The single-nucleotide polymorphism T1151A in the hMLH1 gene might play an etiological role in part of colorectal and gastric cancers in East Asia.