Relation between single nucleotide polymorphism (SNP) of gastric carcinogenesis- and cancer progression -associated genes and peritumoral stromal reaction in early gastric cancer

胃癌发生及进展相关基因单核苷酸多态性（SNP）与早期胃癌瘤周间质反应的关系

• 批准号: 15590303
• 负责人: NAKAYAMA Hirofumi
• 金额: $ 1.98万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590303/
• 关键词: 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

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.

据报道，HER 2基因跨膜区的单核苷酸多态性（Ile/瓦尔，A/G）与乳腺癌的风险相关。因此，HER-2基因多态性与胃癌的关系进行了研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和测序方法分析HER 2基因的SNP。212例胃癌患者中Ile/Ile、Ile/瓦尔和瓦尔/瓦尔基因型分别为146例（68.9%）、56例（26.4%）和10例（4.7%）; 287例对照组中分别为234例（81.5%）、48例（16.7%）和5例（1.8%）。在患者中，Ile/瓦尔或瓦尔/瓦尔基因型患者的晚期癌发生率明显高于Ile/Ile基因型患者（p<0.001）。HER-2基因型与肿瘤浸润、淋巴结转移和远处转移密切相关。HER-2基因多态性与早期胃癌组织间质反应（界限清楚与否）无相关性，但基质金属蛋白酶-9（MMP-9，明胶酶B）启动子-1562位点的胞嘧啶（C）-胸苷（T）单核苷酸多态性（SNP）影响HER-2基因的表达。本研究旨在探讨-1562 C/T多态性与胃癌发生、发展的关系。研究了基因型与临床病理特征的关系。胃癌患者MMP-9基因多态性与肿瘤浸润程度、临床分期、淋巴管浸润密切相关（均P<0.05），提示MMP-9基因启动子区T等位基因与胃癌浸润表型相关。MMP-9基因启动子多态性与早期胃癌肿瘤边缘间质反应无关，死亡受体4（DR 4）基因多态性与早期胃癌肿瘤边缘间质反应无关。

项目成果

Kuraoka K: "Correlation of a sibgle nucleotide polymorphism in the E-cadherin gene promoter with tumorigenesis and progression of gastric carcinoma in Japan"International Journal of Oncology. 23・2. 421-427 (2003)

Kuraoka K：“E-钙粘蛋白基因启动子中的单核苷酸多态性与日本胃癌发生和进展的相关性”国际肿瘤学杂志23·2（2003）。

Ito R: "Expression of Cb1 linking with EGFR system is associated with tumor progression and poor prognosis of human gastric carcinoma"Virchows Archiv. in press. (2004)

Ito R：“与 EGFR 系统连接的 Cb1 的表达与人胃癌的肿瘤进展和不良预后相关”Virchows Archiv。

Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma

• DOI: 10.1002/ijc.20521
• 发表时间: 2004-12-20
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Oshimo, Y;Kuraoka, K;Yasui, W
• 通讯作者: Yasui, W

A single nucleotide polymorphism in the extracellular domain of TRAIL receptor DR4 at nucleotide 626 in gastric cancer patients in Japan.

• DOI: 10.3892/or.14.2.465
• 发表时间: 2005-08
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: K. Kuraoka;Shunji Matsumura;Y. Sanada;K. Nakachi;K. Imai;H. Eguchi;K. Matsusaki;N. Oue;H. Nakayama;W. Yasui

Correlation of a single nucleotide polymorphism in the E-cadherin gene promoter with tumorigenesis and progression of gastric carcinoma in Japan.

• DOI: 10.3892/ijo.23.2.421
• 发表时间: 2003-08
• 期刊: International journal of oncology
• 影响因子: 5.2
• 作者: K. Kuraoka;N. Oue;H. Yokozaki;Y. Kitadai;R. Ito;H. Nakayama;W. Yasui