The relation of colorectal carcinogenesis with F. nucleatum analysis and the prevention

• Project/Area Number: 18K15788
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Kanno Shinichi 札幌医科大学, 医学部, 研究員 (20782254)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 大腸癌 / F. nucleatum / microbiota / MSI / Probiotics / 免疫応答 / Fusobacterium / non-coding RNA

Outline of Final Research Achievements

The association between highly enriched F. nucleatum in colorectal carcinoma tissues, and MSI-high status was observed in both the U.S. cohort studies and Japanese population-based study. Previous studies have reported that the frequency of colorectal cancers with MSI-high status in Japan (less than 10%） tend to be lower than those in U.S. and Western countries (about 15%). Therefore, the low rate of MSI-high in Japanese colorectal cancer might be due to the amount of F. nucleatum in carcinoma tissues, because our current data showed that the rate of F. nucleatum positivity in Japanese patients was lower than that in the U.S. cohorts.

Academic Significance and Societal Importance of the Research Achievements

本研究は従来までF. nucleatum研究で用いられていない小さな大腸腫瘍とその周囲の正常粘膜の臨床検体をサンプルとする新たな試みである。その成果によりF. nucleatumが正常のヒト大腸粘膜や小さなポリープ内で腫瘍発生・増殖を促していることが示された場合、癌予防におけるF. nucleatumの重要性は高まると考えられる。また米国のコホート研究で食物繊維が豊富な食事がF. nucleatum陽性大腸癌のリスクを低下させるとの報告がなされたことで、F. nucleatumを標的とした大腸癌予防の現実味は増しており、本研究の動物実験の成果はヒトへの介入研究の礎の一つとなることが期待される。

Research Products

• [Journal Article] 大腸癌とFusobacterium－Serrated pathwayとの切り口から (2018)
  • Author(s): 能正勝彦、菅野伸一、仲瀬裕志
  • Journal Title: 消化器・肝臓内科 Volume: 4 Pages: 375-381
• [Journal Article] Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression (2018)
  • Author(s): Eto T, Miyake K, Nosho K, Ohmuraya M, Imamura Y, Arima K, Kanno S, Fu L, Kiyozumi Y, Izumi D, Sugihara H, Hiyoshi Y, Miyamoto Y, Sawayama H, Iwatsuki M, Baba Y, Yoshida N, Furukawa T, Araki K, Baba H, Ishimoto T
  • Journal Title: The Journal of Pathology Volume: 245 Issue: 4 Pages: 445-455
  • DOI: 10.1002/path.5098
  • Peer Reviewed