| Project/Area Number |
08457317
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Tokyo Medical and Dental University School of Medicine |
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Principal Investigator |
KAWANO Tatsuyuki (1997-1998) Tokyo Medical and Dental University school of Medicine, Assistant Proffiesor, 医学部, 講師 (00186115)
遠藤 光夫 (1996) 東京医科歯科大学, 医学部, 教授 (60075190)
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| Co-Investigator(Kenkyū-buntansha) |
NAPAI Kapami Tokyo Medical and Dental University, Scholl of Medicine, Instructor, 医学部, 助手 (10251505)
河野 辰幸 東京医科歯科大学, 医学部, 助手 (00186115)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1996: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | esophageal carcinoma / heterogeneity / ADH2 / ALDH2 / alcohol / penetic polymorphism / TNF-alpha / TGF-beta RII / TNF-α / IL-1α / IL-1β / IL-1RA / 遺伝子変化 / アルコール代謝 / タバコ / 食道発癌 / 食道扁平上皮癌 / p53 / RER / hMSH2 / hMLH1 / PCR-SSCP |
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| Research Abstract |
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
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