Elucidation of carcinogenic mechanism for serrated polyposis syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08471
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokushima
• Principal Investigator: OKAMOTO Koichi 徳島大学, 病院, 講師 (60531374)
• Co-Investigator(Kenkyū-buntansha): 高山 哲治 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (10284994) ; 中村 文香 徳島大学, 病院, 特任助教 (70793743) ; 六車 直樹 徳島大学, 大学院医歯薬学研究部(医学域), 徳島大学専門研究員 (90325283)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: SPS / メチル化 / 大腸癌 / 腺腫 / 鋸歯状ポリープ

Outline of Final Research Achievements

The prevalence of adenoma in SPS was 73% (32/44) and adenoma was a risk factor for CRCs, suggesting its importance in colorectal carcinogenesis. The incidence of CRC including intramucosal carcinoma in this study was 41% (18/44) and the median (IQR) ages at diagnosis of CRC was 62 years. According to the definition of each pathway, we classified 5 CRCs as originating through the serrated-neoplasia pathway, and 11 through the adenoma-carcinoma pathway. Of the 5 CRCs via the serrated neoplasia pathway, only 1 was a well-reported pathway with both BRAF mutation and MSI-H. Therefore, we should search not only for SSL in the proximal colon but also for adenoma in the distal colorectum, as well as the transverse colon, to remove them.

Free Research Field

大腸発癌　予防

Academic Significance and Societal Importance of the Research Achievements

serrated-carcinoma pathwayから発癌した病変は80%が右側結腸癌であり、adenoma-carcinoma pathwayは78%が左側結腸癌であった。また、serrated-carcinoma pathwayから発癌した病変は全例、SPS診断基準(1)であり、SPからのダイレクトな発癌経路が想定され、adenoma-carcinoma pathwayから発癌した病変の約8割は大腸全体に鋸歯状腫瘍を20個以上有するSPS診断基準(2)を満たしており、大腸粘膜自体の同時多発的なメチル化を背景として、腺腫から癌へと進展する新たな経路が想定された。