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Molecular epidemiological study of oral cancer in Sri Lanka and Taiwan

Research Project

Project/Area Number 16406034
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Surgical dentistry
Research InstitutionGifu University

Principal Investigator

SHIBATA Toshiyuki  Gifu University, GRADUATE SCHOOL OF MEDICINE, Professor (50226172)

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)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥13,930,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥930,000)
Fiscal Year 2007: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsORAL CANCER / CARCINOGENESTS / BETEL CHEWING / MOLECYLAR ANALYSIS / SRI LANKA
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 … More 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

Report

(5 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2008 2007 2006 2005 2004 Other

All Journal Article (35 results) (of which Peer Reviewed: 9 results) Presentation (3 results)

  • [Journal Article] High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka2008

    • Author(s)
      M Takeshima, et. al. I Chiba, T Shibata, Y Abiko
    • Journal Title

      J Oral Pathology and Medicine (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hypermethylation of the RECK gene predicts poor prognosis in oral squamous cell carcinomas2008

    • Author(s)
      NK Long, K Kato, T Yamashita, et. al., T Shibata
    • Journal Title

      Oral Oncology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] High frequency of hypermethylation of p14, p15 and p16 in oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka2008

    • Author(s)
      M. Takeshima, et. al., I. Chiba, T. Shibata, Y. Abiko
    • Journal Title

      J Oral Pathology and Medicine (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hypermethylation of the RECK gene predicts poor prognosis in oral squamous cell carcinomas2008

    • Author(s)
      NK. Long, K. Kato, T. Yamashita, et. al. T. Shibata
    • Journal Title

      Oral Oncology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression pattern of p63 in oral epithelial lesions and submucous fibrosis associated with betel-quid chewing in Sri Lanka2007

    • Author(s)
      AM Haniffa, Y Abiko, et. al. I Chiba, T Shibata
    • Journal Title

      Med Mol Morphol 40(4)

      Pages: 203-207

    • NAID

      10024380380

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] RT-PCR-based cytochrome P450 expression profile of oral tissue samples2007

    • Author(s)
      Sarikaya D, Chiba I, Bilgen C, Kamatakii T, Topcu Z
    • Journal Title

      J Clin Pharm Ther 32

      Pages: 445-448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Chemopreventive effect of fermented brown rice and rice bran on 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats2007

    • Author(s)
      Nguyen KL, Makita H, Yamashita T, Toida M, Kato K, et. al., Shibata T
    • Journal Title

      Oncol Rep 17

      Pages: 879-885

    • NAID

      120006340780

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis2007

    • Author(s)
      Makita H, Yonemoto K, Kobayashi A, Toida M, shibata T, et. al.
    • Journal Title

      Carcinogenesis 28

      Pages: 677-684

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression pattern of p63 in oral epithelial lesions and submucous fibrosis associated with betel-quid chewing in Sri Lanka2007

    • Author(s)
      AM. Haniffa, Y. Abiko, et. al., I., Chiba, T. Shibata
    • Journal Title

      Med Mol Morphol 40(4)

      Pages: 203-207

    • NAID

      10024380380

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] RT-PCR-based cytochrome P450 expression profile of oral tissue samples2007

    • Author(s)
      Sarikaya, D., Chiba, I., Bilgen, C., Kamatakii, T., Topcu, Z
    • Journal Title

      J Clin Pharm Ther 32

      Pages: 445-448

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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
    • Journal Title

      Oncol Rep 17

      Pages: 879-885

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [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.
    • Journal Title

      Carcinogenesis 28

      Pages: 677-684

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis2007

    • Author(s)
      Makita H, Mutoh M, Maruyama T, Yonemoto K, Kobaynshi A, Fujituka H, Toida M, shibata T, Miyamoto S, Yasui Y, Suzuki R, Wkabayashi K, Tanaka T
    • Journal Title

      Carcinogenesis 28

      Pages: 677-684

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chemopreventive effect of fermented brown rice and rice bran on 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats.2007

    • Author(s)
      Nguyen K L, Makita H, Yamashita T, ToidaM, Kato K, Hatakeyama D, Shibata T
    • Journal Title

      Oncol Rep 17

      Pages: 879-885

    • NAID

      120006340780

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa.2006

    • Author(s)
      Kato K, Hara A, Kuno T, Mori H, Yamashita T, Toida M, Shibata T
    • Journal Title

      J Cancer Res Clin Oncol 132

      Pages: 735-743

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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.
    • Journal Title

      Oncol Rep 15

      Pages: 757-763

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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.
    • Journal Title

      Oncol Rep 15

      Pages: 757-763

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Novel ideas of gene therapy for atherosclerosis : modulation of cellular signal transduction of TGF-b family.2006

    • Author(s)
      Akira Ishisaki, Hiroyuki Matsuno.
    • Journal Title

      Curr. Pharm. Design 12

      Pages: 877-886

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitory effects of fermented brown rice and rice bran on the development of acute hepatitis in Long-Evans Cinnamon rats2006

    • Author(s)
      Shibata T, Nagayasu H, Kitajo H, Arisue M, Yamashita T, Hatakeyama D, Iwasaki T, Kobsyashi H.
    • Journal Title

      Oncol Rep. 15

      Pages: 736-743

    • NAID

      120006340757

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Aberrant promoter hypermethylation of p16 and MGMT genes in oral squamous cell carcinomas and the surrounding normal mucosa2006

    • Author(s)
      Kato K, Hara A, Kuno T, Mori H, Yamashita T, Toida M, Shibata T.
    • Journal Title

      J Cancer Res Clin Oncol. 132

      Pages: 735-743

    • Related Report
      2006 Annual Research Report
  • [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, Takami T.
    • Journal Title

      Oncol Rep. 5

      Pages: 757-763

    • Related Report
      2006 Annual Research Report
  • [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 Mori H, Toida M, Shibata T.
    • Journal Title

      J Cancer Res Clin Oncol 131

      Pages: 340-346

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [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
    • 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
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Analysis of ameloblastomas by comparative genomic hybridization and fluorescence in situ hybridization2005

    • Author(s)
      Toida M, Balazs M, et al.-7, Shibata T.Adany R.
    • Journal Title

      Cancer Genet Cytogenet. 159

      Pages: 99-104

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats.2005

    • Author(s)
      Yoshida K, Tanaka T, et al.--6, Shibata T, Mori H.
    • Journal Title

      Cancer Lett. 221

      Pages: 29-39

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinical value of genetically diagnosed lymph node micrometastasis for patients with oral squamous cell carcinoma.2005

    • Author(s)
      Yamazaki Y, Chiba I, et al., -4
    • Journal Title

      Head Neck. 27

      Pages: 676-681

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adenylyl cyclase-cAMP system inhibits thyroid hormone-stimulated osteocalcin synthesis in osteoblasts.2005

    • Author(s)
      Yosuke Kanno, Akira Ishisaki, et al.-4.
    • Journal Title

      Mol.Cell.Endocrinol 229

      Pages: 75-82

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PPAR-gamma ligands up-regulate basic fibroblast growth factor-induced VEGF release through amplifying SAPK/JNK activation in osteoblasts.2005

    • Author(s)
      Eisuke Yasuda, Haruhiko Tokuda, Akira Ishisaki, et al.-7
    • Journal Title

      Biochem.Biophys.Res.Commun 328

      Pages: 137-143

    • Related Report
      2005 Annual Research Report
  • [Journal Article] αB-crystallin is phosphorylated during myocardial infarction : Involvement of platelet-derived growth factor-BB.2005

    • Author(s)
      En Shu, Hiroyuki Matsuno, Shigeru Akamastu, Yosuke Kanno, Hidetaka Suga, Keiichi Nakajima, Akira Ishisaki. et al.-3
    • Journal Title

      Arch.Biochem.Biophys 438

      Pages: 111-118

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of Ameloblastomas by comparative genomic hybridization and fluorescence in situ hybridyzation2005

    • Author(s)
      M.Toida, M.Balazs, A.Treszl, T.Shibata, R.Adany
    • Journal Title

      Cancer Genetics and Cytogenetics (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Matrix matalloproteinase 2 and 9 in oral squamous cell carcinomas : manifestation and localization of their activity2005

    • Author(s)
      K.Kato, T.Shibata, et al.
    • Journal Title

      Journal of cancer research and clinical oncology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Involvement of SAPK/JNK in prostaglandin E1-induced VEGF synthesis in osteoblast-like cells.2004

    • Author(s)
      Y.Kanno, H.Tukuda, K.Nakajima, A.Ishisaki, T.Shibata, O.Kozawa
    • Journal Title

      Molecular and Cellular Endocrinology 220

      Pages: 89-95

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intra-articular oxidative state correlated with the pathogenesis of disorders of the temporomandibular joint.2004

    • Author(s)
      M.Tomida, J.-I.Ishimaru, M.Kurachi, S.Era, T.Shibata
    • Journal Title

      British J Oral and Maxillofacial Surgery 42

      Pages: 405-409

    • Related Report
      2004 Annual Research Report
  • [Journal Article] がんの化学予防:口腔がん2004

    • Author(s)
      柴田敏之
    • Journal Title

      最新医学 59巻11号

      Pages: 2447-2453

    • Related Report
      2004 Annual Research Report
  • [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
    • 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
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Methylations of p15 and p16 in oral pre-cancers of betel quid chewers in Sri Lanka2007

    • Author(s)
      C Sugiura, I Chiba, et. al., T Shibata
    • Organizer
      89回 アメリカ口腔外科学会総会(AAOMS)
    • Place of Presentation
      Honolulu City
    • Year and Date
      2007-09-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Methylations of p15 and p16 in oral pre-cancers of betel quid chewers in Sri Lanka2007

    • Author(s)
      C. Sugiura, I. Chiba, et. al. T. Shibata
    • Organizer
      89th Annual meeting of American Oral and Maxillofacial Surgery (AAOMS)
    • Place of Presentation
      Honolulu
    • Year and Date
      2007-09-10
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Methylations of p15 and p16 in oral pre-cancers of betel quid chewers in Sri Lanka2007

    • Author(s)
      C Sugiura, I Chiba, et. al., T Shibata
    • Organizer
      89回アメリカ口腔外科学会総会(AAOMS)
    • Place of Presentation
      Honolulu City
    • Year and Date
      2007-09-10
    • Related Report
      2007 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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