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

我们研究了几个实验来阐明食管肿瘤的发生。我们检测了食管鳞状细胞癌的分子克隆异质性。24例食管鳞状细胞癌和相关淋巴结转移的微卫星改变，和异常的p53和转化生长因子β II型受体（TGF-β RII）基因进行了检查。有8例（33%）在原发肿瘤和转移淋巴结中显示不同的微卫星标记杂合性丢失模式。另一方面，p53的异常在所有这些病例中是相同的。在TGF-β RII基因的简单重复序列中未检测到突变。这些结果表明，分子克隆异质性存在于食管鳞状细胞癌。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。我们检查了遗传多态性， 关于我们 94名日本食管鳞状细胞癌患者和70名无关健康日本人的CYPIA 1、GSTMI、CYPIE 1、ADH 2和ALDH 2基因的多态性。CYPIAI、GSTMI和CYPIIE 1基因多态性在健康对照组和食管癌患者之间无显著差异。另一方面，ADH 2和ALDH 2的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ADH 21/ADH 21和ALDH 21/ALDH 22基因型独立且显著高于健康对照组，TNF-α基因多态性与酒精性肝病相关。因此，我们以类似的方式检测了TNF-α、IL-1 α、IL-1 β和IL-1 RA的遗传多态性。ADH 2和ALDH 2基因多态性在食管癌患者和健康对照组之间差异无统计学意义，提示ADH 2和ALDH 2基因多态性可用于食管癌高危人群的筛查，为食管癌的预防提供依据。少

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