| Project/Area Number |
18K15781
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 腸上皮化生 / ヘリコバクター・ピロリ菌 / 遺伝子変異 / コピー数異常 / 胃癌 / ゲノム異常 / 慢性胃炎 |
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| Outline of Final Research Achievements |
Gastric cancer develops in chronic gastritis mucosa related with Helicobacter pylori infection. To explore the susceptibility of gastric glands to cancer development, we investigated genetic alterations in pure gastric glands. Whole-exome sequencing of single gastric glands revealed significantly higher accumulation of somatic mutations in intestinal metaplasia glands compared with non-intestinal metaplasia glands. The numbers of somatic mutations in intestinal metaplasia glands were similar to those in intramucosal gastric carcinoma. In addition, clustered glands with intestinal metaplasia had various copy number aberrations whose patterns were similar to those of intramucosal gastric carcinoma. These findings suggest that, in the gastric mucosa inflamed with H. pylori infection, intestinal metaplasia glands expand via acquisition of copy number aberrations, contributing to field cancerization.
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| Academic Significance and Societal Importance of the Research Achievements |
胃癌の多くは、ヘリコバクター・ピロリ菌の感染による慢性胃炎粘膜より発生する。ただし、慢性胃炎をもった人のうち胃癌が発生するのは一部であり、ピロリ菌の除菌療法後にも胃癌が発生する人もいる。本研究の結果は、ピロリ菌感染による慢性胃炎粘膜に腸粘膜の性質をもつ腸上皮化生が存在すると、胃癌の発生リスクが高いことを示唆する。胃癌のリスク、定期的な内視鏡検査の必要性を考える上で、重要な科学的根拠と考える。
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