| Project/Area Number |
15590303
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
NAKAYAMA Hirofumi Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (50253068)
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| Co-Investigator(Kenkyū-buntansha) |
YASUI Wataru Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (40191118)
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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 |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | gastric cancer / early gastric cancer / single nucleotide polymorphism / amino acid substitution / tumor margin / HER2 / MMP-9 / DR4 / 分化度 / MMP9 / 組織型 / EGF / 未分化幹細胞 |
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| Research Abstract |
A single nucleotide polymorphism(SNP) of HER2 gene (Ile/Val,A/G) in the transmembrane domain was reported to be associated with a risk of breast cancer. So association between the HER-2 polymorphism and gastric carcinoma was examined. The SNP in HER2 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and sequencing. The Ile/Ile,Ile/Val and Val/Val genotypes were found in 146(68.9%), 56(26.4%) and 10(4.7%) of 212 gastric cancer patients and in 234(81.5%), 48(16.7%) and 5(1.8%) of 287 control subjects, respectively. In patients, carcinomas of advanced stage were significantly more frequent in patients with Ile/Val or Val/Val genotype than those with Ile/Ile genotype (p<0.001). Tumor invasion, lymph node metastasis and distant metastasis were closely associated with the HER-2 genotype. There was no correlation between the HER-2 gene polymorphism and stromal reaction (well-circumscribed or not) at the tumor border of early gastric cancer.
A cytosine(C)-thymidine(T) single nucleotide polymorphism(SNP) at position -1562 in the Matrix metalloproteinase-9(MMP-9, gelatinase B) promoter is reported to affect expression of this gene. So relation between the -1562 C/T polymorphism and the development and progression of gastric cancer was examined. Association of genotypes with clinicopathological features was studied. Significant association was found between degree of tumor invasion, clinical stage, and lymphatic invasion and the MMP-9 polymorphism in gastric cancer patients (P<0.05, for each), indicating that the T allele in the MMP-9 promoter is associated with the invasive phenotype of gastric cancer. There was no correlation between the MMP-9 gene promoter polymorphism and stromal reaction at the tumor border of early gastric cancer.
There was no correlation between the Death Receptor 4(DR4) gene polymorphism and stromal reaction at the tumor border of early gastric cancer.
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