p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: Results in Japan and comparisons with other countries

Akinori Egashira, Masaru Morita, Yoshihiro Kakeji, Noriaki Sadanaga, Eiji Oki, Takuya Honbo, Mitsuhiko Ohta, Yoshihiko Maehara

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1152-1156
Number of pages5
JournalCancer Science
Volume98
Issue number8
DOIs
Publication statusPublished - Aug 2007

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'p53 Gene mutations in esophageal squamous cell carcinoma and their relevance to etiology and pathogenesis: Results in Japan and comparisons with other countries'. Together they form a unique fingerprint.

Cite this