2007 Fiscal Year Final Research Report Summary
Molecular epidemiological study of oral cancer in Sri Lanka and Taiwan
| Project/Area Number |
16406034
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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 | 海外学術 |
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| Research Field |
Surgical dentistry
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| Research Institution | Gifu University |
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Principal Investigator |
SHIBATA Toshiyuki Gifu University, GRADUATE SCHOOL OF MEDICINE, Professor (50226172)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Itsuo HEALTH SCIENCES UNIVERSITY OF HOKKAIDO, SCHOOL OF DENTISTRY, Professor (50250460)
TOIDA Makoto GIFU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR (90313890)
YAMASHITA Tomomi GIFU UNIVERSITY, HOSPITAL, LECTURER (80345793)
ISHISAKI Akira HOKKAIDO UNIVERSITY, GRADUATE SCHOOL OF DENIISTRY, ASSOCIATED PROFESSOR (20356439)
MAKITA Hiroki GIFU UNIVERSITY, HOSPITAL, LECTURER (50345790)
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| Project Period (FY) |
2004 – 2007
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| Keywords | ORAL CANCER / CARCINOGENESTS / BETEL CHEWING / MOLECYLAR ANALYSIS |
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| Research Abstract |
Oral squamous cell carcinoma and the most common oral premalignancies such as leukoplakia and oral submucous fibrosis appear to be related to the habit of betel quid chewing in South Asian countries including Sri Lanka and Taiwan. In this study, we carried out the molecular epidemiological analysis of oral cancer and related diseases to reveal the role of genetic and epigenetic backgrounds.
We revealed the genetic changes such as p53 mutations and polymorphism CYP2A6, GSTM1, which could play an important role of carcinogenesis in the oral cancer. Especially, mutation of p53 gene was found out in the Exon 5 intensively and these phenomenon was not observed in the pre-cancerous lesions. These results strongly suggested that the one hit of the gene might not read the cancer lesion. DNA analysis of these patients indicated that polymorphisms of CYP2A6 (nitrosoamine activating enzyme) and GSTM1 (activated nitrosoamine metabolic enzyme) might be the candidates of the genetic background of the
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betel quid related diseases. Furthermore, epigenetic changes such as hypermethylation of tumor suppressor gene p15 and p16 and/or DNA repairing gene MGMT was investigated. In epithelial dysplasia and oral submucous fibrosis, the frequency of hypermethylation of p15 and p16 was significantly higher than those in normal epithelium. Betel quid chewing may cause p15 and p16 hypermethylation and metylation status of these genes was associated with epithelial dysplasia and their severity. This phenomenon was observed in the Japanese oral cancer, precancer lesions and also detected in the pathological normal tissues and the alcohol and /or smoking habit population frequently. Therefore, the hypermethylation of these genes may cause and associate with the oral cancer and disease development. Furthermore, these abnormalities of the DNA methylation status highly observed in the alcohol and /or smoking consumption population was possibly seemed to be one of the useful biomaker to evaluate the oral mucosa condition.
In conclusion, these detections including genetic changes may be useful as not only a diagnostic tool for transformation and risk analysis, but also evaluating tool for the oral mucosal health conditions and prediction of the diseases. Less
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[Journal Article] Chemopreventive effect of fermented brown rice and rice bran on 4-nitroquinoline l-oxide-induced oral carcinogenesis in rats2007
Author(s)
Nguyen, KL., Makita, H., Yamashita, T.,Toida, M., Kato, K., et. al., Shibata, T
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Journal Title
Oncol Rep 17
Pages: 879-885
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A prostaglandin E2 receptor subtype EP I-selective antagonist, ONO-8711, suppresses 4-nitroquinoline I-oxide-induced rat tongue carcinogenesis2007
Author(s)
Makita, H., Yonemoto, K., Kobayashi, A., Toida, M., shibata, T., et. al.
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Journal Title
Carcinogenesis 28
Pages: 677-684
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Preoperative radiotherapy contributes to induction of proliferative activity of CD8+ tumor-infiltrating T-cells in oral squamous cell carcinoma2006
Author(s)
Suwa, T., Saio, M., Umemura, N., Yamashita, T., Toida, M., Shibata, T., et. al.
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Journal Title
Oncol Rep 15
Pages: 757-763
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Matrix metalloproteinase-2, and 9 in oral squamous cell carcinomas ; manifestation and localization of their activity2005
Author(s)
Kato, K., Hara, A., Kuno, T., Kitaori, N., Huilan, Z., Mori, H., Toida, M., Shibata, T
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Journal Title
J Cancer Res Clin Oncol 131
Pages: 340-346
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa
Author(s)
Kato, K., Hara, A., Kuno, T., Mon, H., Yamashita, T., Toida, M., Shibata, T
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Journal Title
J Cancer Res Clin Oncol 132
Pages: 735-743
Description
「研究成果報告書概要(欧文)」より
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