Analysis of CDH1 Pathological Germ Cell Variants and Environmental Factors - Application to Diffuse Gastric Cancer Prevention

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15512
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Yokohama City University
• Principal Investigator: SUZUKI Akihiro 横浜市立大学, 医学研究科, 客員講師 (80869222)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胃がん / CDH1

Outline of Final Research Achievements

Gastric cancer is generally classified into diffuse-type gastric cancer, which has a poor prognosis, and intestinal-type gastric cancer, which has a relatively good prognosis. With the development of endoscopic techniques, early detection and treatment have become possible, and the prognosis of intestinal-type gastric cancer has improved dramatically.
The applicant is a Japanese patient with large genomes of gastric cancer. The applicant performed a large-scale genome analysis of Japanese gastric cancer and revealed several germline gene mutations associated with carcinogenesis of diffuse-type gastric cancer (Suzuki et al., Science Advances, 2020). In this study, we focus on CDH1 among the genes identified in this analysis as being associated with carcinogenesis of diffuse-type gastric cancer, aiming to stratify risk factors for diffuse-type gastric cancer using CDH1 and apply it to preventive medicine in the future.

Free Research Field

胃がん

Academic Significance and Societal Importance of the Research Achievements

びまん型胃癌は内視鏡検査による早期発見・早期治療が困難であり、依然として予後不良癌の代表格である。代表者は日本人胃癌の大規模ゲノム解析を行い、びまん型胃癌の発癌と関連する生殖細胞系列の遺伝子変異を複数明らかにした（Suzuki et al., Science Advances, 2020）。この解析で明らかにしたびまん型胃癌の発癌と関連する遺伝子の内、CDH1に着目する。申請者は、びまん型胃癌の発がんと関連する5種類の生殖細胞系列のCD1H変異（病的胚細胞バリアント）を明らかにしたが、それらの機能的な解析は行えていない。解析することで将来的なびまん性胃癌の予防の足掛かりを作ることができる。