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Analysis of geneticalteration in esophapeal sfuamos cell carcinoma and application to clincal diapnosis

食管鳞状细胞癌基因突变分析及其在临床诊断中的应用

基本信息

批准号：
08457317
负责人：
KAWANO Tatsuyuki
金额：
$ 4.48万
依托单位：
Tokyo Medical and Dental University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

We studied several experiments to clarify esophageal tumorigenesis.We examined molecular clonal heterogeneity in esophageal squamous cell carcinomas. Twenty-four esophageal squamous cell carcinomas and associated lymph node metastases were examined for microsatellite alterations, and abnormalities of the p53 and transforming growth factor-beta type II receptor (TGF-beta RII) genes. There were eight cases (33%) showing different patterns of loss of heterozygosity in primary tumors and metastatic lymph nodes with microsatellite markers. On the other hand, the abnormalities of p53 were identical in all these cases. No mutation was detected in the simple repeated sequences of the TGF-beta RII gene. These results indicate that molecular clonal heterogeneity exists in esophageal squamous cell carcinomas We studied the association between genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and esophageal squamous cell carcinoma susceptibility. We examined genetic polymo … More rphisms of the CYPIAl, GSTMI, CYPIIEl, ADH2 and ALDH2 genes in 94 Japanese esophageal squamous cell carcinoma patients and 70 unrelated healthy Japanese. There were no significant differences between healthy controls and esophageal cancer patients in the polymorphisms of the CYPIAI, GSTMI and CYPIIEl genes. On the other hand, there were significant differences in the ADH2 and ALDH2 polymorphisms between healthy controls and esophageal cancer patients. The ADH21/ADH21 and ALDH21/ALDH22 genotypes wen independently and significantly higher in esophageal cancer patients than in healthy controls.It was reported that the polymorphism of the TNF- alpha related to alcoholic liver disease. Therefore we examined genetic polymorphisms of the TNF-alpha, IL-1 alpha, IL-1 beta and IL-1RA in a similar way. However there were no significant differences between healthy controls and esophageal cancer patients in those polymorphisms.Polymorphisms of ADH2 and ALDH2 may be useful for the screening of high risk for esophageal cancer which might facilitate prevention of esophageal cancer. Less

我们研究了几个实验来阐明食道肿瘤的发生。我们研究了食管鳞状细胞癌的分子克隆异质性。我们检测了24例食管鳞状细胞癌和相关淋巴结转移灶的微卫星改变，以及p53和转化生长因子- β II型受体（tgf - β RII）基因的异常。有8例（33%）在原发肿瘤和转移性淋巴结中表现出不同模式的杂合性缺失。另一方面，p53的异常在所有这些病例中都是相同的。tgf - β RII基因的简单重复序列未检测到突变。我们研究了烟草和酒精相关代谢酶基因多态性与食管鳞状细胞癌易感性的关系。我们检测了94例日本食管鳞癌患者和70例无亲缘关系的日本人的CYPIAl、GSTMI、CYPIIEl、ADH2和ALDH2基因的多态性。正常对照组与食管癌患者CYPIAI、GSTMI和CYPIIEl基因多态性差异无统计学意义。另一方面，ADH2和ALDH2多态性在健康对照组和食管癌患者之间存在显著差异。食管癌患者ADH21/ADH21和ALDH21/ALDH22基因型独立且显著高于健康对照组。据报道，TNF- α多态性与酒精性肝病有关。因此，我们以类似的方式检测了tnf - α， IL-1 α， IL-1 β和IL-1RA的遗传多态性。然而，这些多态性在健康对照组和食管癌患者之间没有显著差异。ADH2和ALDH2基因多态性可能有助于食管癌高危人群的筛查，有助于食管癌的预防。少