The role of expression and polymorphism of metabolic enzymes in the smoking-or alcohol-induced carcinogenesis of the esophagus and the lung
| Project/Area Number |
15591460
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
MORITA Masaru University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 講師 (30294937)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIO Kenji University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (70235927)
OYAMA Tsunehiro University of Occupational and Environmental Health, School of Medicine, Associate Professor, 医学部, 助教授 (00309965)
HANAGIRI Takeshi University of Occupational and Environmental Health, School of Medicine, Assistant Professor, 医学部, 講師 (30299614)
竹之山 光広 産業医科大学, 医学部, 助手 (10309966)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Esophageal cancer / Lung cancer / Multiple cancer / Alcohol drinking / Cigarette smoking / Aldehyde dehydrogenase / Fhit / p16 |
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| Research Abstract |
Environmental factors such as cigarette smoking and alcohol drinking are important in the development of lung cancer as well as esophageal cancer. Most carcinogens are not carcinogenic per se, and the metabolic activation is required to act as carcinogens. Therefore, metabolic enzymes to activate or detoxify are reported to play an important role in exogenously induced carcinogenesis. The polymorphism of these metabolic enzymes is considered to be associated with susceptibility to these cancers. For example, inactive aldehyde dehydrogenase 2 (ALDH2) is a risk factor of esophageal cancer. In order to clarify the role of the expression of these enzymes as well as the molecular targets of risk factors, we have performed researches. 1) The expression of ALDH2 was closely associated with drinking status and flushing after drinking. Therefore, the genetic status of ALDH2 as well as alcohol consumption must be important in the expression of ALDH2 in the esophagus. 2) In order to evaluate the usefulness of Aldh2-null mice, the tissue-distribution of ALDH2 in wild mice was examined and it found to be similar with that of human. Therefore, Aldh2-null mice are considered to be useful model animals for investigation of alcohol metabolism and related diseases. 3) Fhit loss in the normal esophagus is closely associated with drinking habits as well as multiplicity of esophageal cancer. 4) Regarding lung cancer, the methylation of p63 were frequently observed in heavy smoker and patients with squamous cell carcinoma. Therefore, methylation of p 16 may play an important role in smoking-induced lung carcinogenesis.
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Report
(3 results)
Research Products
(18 results)
