Molecular mechanism of esophageal carcinogenesis induced by cigarette smoking and alcohol drinking and its clinical application

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591966
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: National Hospital Organization, Kyushu Cancer Center (2014); Kyushu University (2012-2013)
• Principal Investigator: MORITA Masaru 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, その他 (30294937)
• Co-Investigator(Kenkyū-buntansha): TOH Yasushi 国立病院機構九州がんセンター, 臨床研究センター, 副院長 (20217459) ; SAKAGUCHI Yoshihisa 国立病院機構九州医療センター, 臨床研究センター, 消化器外科部長 (00215625) ; OKI Eiji 九州大学, 医学(系)研究科(研究院), 准教授 (70380392) ; SAEKI Hiroshi 九州大学, 大学病院, 講師 (80325448)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 食道癌 / 喫煙 / 飲酒 / 癌抑制遺伝子 / 染色体不安定性 / 酸化的DNAs損傷 / 酸化ストレス / メチル化

Outline of Final Research Achievements

The purpose is to clarify mechanism of esophageal carcinogenesis induced by cigarette smoking and alcohol drinking.
1) The expression of 8-OHdG (a marker of oxidative stress) and that of its repair enzyme, OGG1 were immunohistochemically evaluated in esophageal specimens. The expression of 8-OHdG was related to smoking index. The expressions of OGG-1 were related to 8-OHdG in normal mucosa, while this correlation was not observed in the cancer. Oxidative DNA damage, which is attributable to smoking as well as disturbances in DNA repair systems, appears to be closely related to esophageal carcinogenesis.
2) LINE-1 methylation levels of normal esophageal mucosa had the inverse correlation with both cigarette smoking and alcohol consumption. LINE-1 methylation of esophageal cancer had the inverse association with the chromosomal instability. The whole genome hypomethylation caused by chronic inflammation could initiate the esophageal carcinogenesis through chromosomal instability.

Free Research Field

消化器外科