Analysis of risk factors for gastric cancer in order to construct tailor-made medicine for gastric cancer
| Project/Area Number |
15390231
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Fukui (2004)
福井医科大学 (2003) |
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Principal Investigator |
AZUMA Takeshi University of Fukui, Faculty of Medical Sciences, Associate Professor, 医学部, 助教授 (60221040)
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| Co-Investigator(Kenkyū-buntansha) |
TATEMATSU Masae Aichi Cancer Center Research Institute, Division of Oncological Pathology, Chief, 腫瘍病理学, 部長 (70117836)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2003: ¥10,100,000 (Direct Cost: ¥10,100,000)
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| Keywords | H.pylori / CagA / Gastric cancer / オーダーメイド医療 |
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| Research Abstract |
After attachment of cagA-positive H. pylori to gastric epithelial cells, CagA is directly injected from the bacteria into the cells via the bacterial type IV secretion system and undergoes tyrosine phosphorylation in the host cells. We recently discovered that translocated CagA forms a physical complex with SHP-2. SHP-2 is known to play an important positive role in mitogenic signal transduction. Deregulation of SHP-2 by CagA may induce abnormal proliferation of gastric epithelial cells. In addition, the CagA protein is polymorphic. We discovered that predominant CagA proteins isolated in East Asia, where gastric cancer is prevalent, have a distinct sequence at the phosphorylation site of CagA. East Asian-specific sequence confers stronger SHP-2 binding and transforming activities to Western CagA. The diversity of the CagA phosphorylation site, which collectively determines binding affinity of CagA to SHP-2, may be an important variable in determining the clinical outcome of infection. We examined the CagA diversity of H. pylori isolated from patients with chronic gastritis or gastric cancer in Japan. The prevalence of East Asian CagA was significantly higher in patients with gastric cancer than in patients with chronic gastritis. The risk for gastric cancer associated with East Asian CagA-positive H. pylori infection was 11.8 (95% confidence limits, 7.33 to 383.31). Endemic circulation of H. pylori populations with more virulent East Asian CagA proteins may affect the prevalence of gastric cancer.
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Report
(3 results)
Research Products
(12 results)
