Association carcinogenesis with oral microbiota in colorectal cancer

• Project/Area Number: 17K10629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: Kondo Satoru 三重大学, 医学部附属病院, 医員 (60763737)
• Co-Investigator(Kenkyū-buntansha): 問山 裕二 三重大学, 医学系研究科, 准教授 (00422824) ; 奥川 喜永 三重大学, 医学部附属病院, 講師 (30555545) ; 楠 正人 三重大学, 医学系研究科, 教授 (50192026)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 大腸癌 / 潰瘍性大腸炎 / 腸内細菌 / マイクロサテライト不安定性 / 潰瘍性大腸炎関連癌 / 腸内細菌叢 / 遺伝子解析 / 口腔内細菌叢

Outline of Final Research Achievements

Specific miRNAs to be methylated and DMRs in rectal mucosal in patients with UC could be used to identify patients with UC at greatest risk for developing UC-CRC. Fusobacterium infection was detected in CRC tissues. Furthermore, Fusobacterium infection was significantly associated with MSI-H compared to non-MSI-H. Unfortunately, it is difficult to detect the oral microbiota and we could not process comprehensive analysis of oral microbiota.

Academic Significance and Societal Importance of the Research Achievements

本研究結果を用いることで、潰瘍性大腸炎患者における潰瘍性大腸炎関連大腸癌の発癌予測マーカーとなり得るほか、MSI－H大腸癌における発癌機序に腸内細菌が関与している新たな可能性が示唆された。

Research Products

• [Journal Article] Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from ulcerative colitis patients with neoplasia. (2018)
  • Author(s): Toiyama Y, Okugawa Y, Kondo S, Okita Y, Araki T, Kusunoki K, Uchino M, Ikeuchi H, Hirota S, Mitsui A, Takehana K, Umezawa T, Kusunoki M.
  • Journal Title: Oncotarget. Volume: 4 Issue: 69 Pages: 33149-33159
  • DOI: 10.18632/oncotarget.26032
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Panel of Methylated MicroRNA Biomarkers for Identifying High-Risk Patients With Ulcerative Colitis-Associated Colorectal Cancer. (2017)
  • Author(s): Toiyama Y, Okugawa Y, Tanaka K, Araki T, Uchida K, Hishida A, Uchino M, Ikeuchi H, Hirota S, Kusunoki M, Boland CR, Goel A
  • Journal Title: Gastroenterology Volume: 153 Pages: 1634-1646
  • Peer Reviewed
• [Presentation] FUSOBACTERIUM NUCLEATUM INFECTION ASSOCIATES WITH TWO TYPES OF MICROSATELLITE ALTERATIONS IN COLORECTAL CANCERS (CRC) (2019)
  • Author(s): Minoru Koi, Yoshiki Okita, Yoshinaga Okugawa, Takahito Kitajima, Yuji Toiyama, Erika Koeppe, Elena M Stoffel, John M Carethers
  • Organizer: Digestive Disease Week 2019
  • Int'l Joint Research
• [Presentation] クローン病術後の抗TNF-α抗体の維持治療についての検討 (2017)
  • Author(s): 近藤 哲、荒木俊光、大北喜基、沖 哲、今岡裕基、北嶋貴仁、松下航平、藤川裕之、安田裕美、小池勇樹、奥川喜永、吉山繁幸、廣 純一郎、井上幹大、小林美奈子、大井正貴、問山裕二、内田恵一、楠 正人
  • Organizer: 第72回日本大腸肛門病学会学術集会、福岡、2017.11.10