p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis:: Results in Japan and comparisons with other countries
p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis:: Results in Japan and comparisons with other countries
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DOI：
10.1111/j.1349-7006.2007.00524.x
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发表时间：
2007-08-01
期刊：
影响因子：
5.7
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Egashira, Akinori;Morita, Masaru;Maehara, Yoshihiko
食管鳞状细胞癌是一种癌症，在不同国家、不同地理区域和不同种族群体中具有不同的发病率。根据先前的报道，在这些肿瘤中的20-80%中已经确定了p53基因突变，并且这些突变发生在早期阶段。这些发现表明，这种突变在食管癌发生中起着重要作用，并强调了诱变剂的重要性，这会导致p53基因序列的改变。为了阐明食管癌发生过程中特定突变的发生和预防的环境因素和分子机制，我们分析了95例食管鳞状细胞癌中p53基因突变。我们进一步回顾了已发表的研究食管癌中p53基因突变频率的报告，并将这些结果与我们在日本的结果进行了比较。日本食管癌中p53基因突变的频率为47.4%，有三个突出特征：（1）颠换占优势，特别是G：C至T：A颠换;（2）转换频率相对较低;（3）移码突变百分比相对较高。这些结果表明，苯并[a]芘代谢产物和氧化性DNA损伤在食管癌发生中可能具有重要意义，与其他胃肠道癌症相比，与DNA复制错误或烷基化几乎没有相关性。此外，我们观察到一个特殊的移码突变序列。总之，这些数据表明，该抑癌基因在食管鳞状细胞癌的多步骤癌变过程中起着关键作用。
Esophageal squamous cell carcinoma is a form of cancer that has varying incidence rates among different countries, distinct geographic areas and different ethnic groups. According to previous reports, p53 gene mutations have been identified in 20-80% of these tumors, and these mutations have occurred at an early stage. These findings suggest that such mutations play an important role in esophageal carcinogenesis, and highlight the importance of mutagens, which cause sequence alterations in the p53 gene. In order to clarify the environmental factors and the molecular mechanisms that may be responsible for the occurrence and prevention of a specific mutation in the process of esophageal carcinogenesis, we analyzed p53 gene mutations in 95 samples of esophageal squamous cell carcinoma. We further reviewed published reports investigating the frequency of p53 gene mutations in esophageal cancer from high-risk areas to normal-risk areas and compared these findings to our results in Japan. The frequency of p53 gene mutations in Japanese esophageal cancer is 47.4% and there are three prominent features: (1) a predominance of transversions, in particular the G:C to T:A transversion; (2) a relatively low frequency of transitions; and (3) a relatively high percentage of frameshift mutations. These results indicate the possible importance of the benzo[a]pyrene metabolite and oxidative DNA damage in esophageal carcinogenesis and scarcely correlate with DNA replication errors or alkylation in comparison to other gastrointestinal cancers. In addition, we observed a peculiar sequence of frameshift mutations. Taken together, these data suggest that this tumor suppressor gene plays a critical role in the multistep carcinogenesis process for esophageal squamous cell cancer.