Molecular pathological study of individual predisposition to gastric cancer

胃癌个体易感性的分子病理学研究

• 批准号: 15390125
• 负责人: SUGIMURA Haruhiko
• 金额: $ 9.66万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390125/
• 关键词: gastric cancer; molecular epidemiology; genetic predisposition; genetic polymorphism; oxidative DNA damage; multiple gastric cancer; GI tract cancer; FISH; 胃癌; 胃癌感受性; 胃癌家系; ハプロタイプ; Peutz-Jeghers症候群; CDH1; 家族性胃癌; 遺伝統計; ミニサテライト; 連鎖解析; Peut

The following results were obtained during the above period.1.Mis-sense germline mutation of CDH1 in Japanese familial gastric cancer subjects.2.The investigator clarified that OGG1 polymorphism modified the life style dependent risk of upper GI tract cancer.3.A new method to detect chromosomal instability in pathology archives of gastric cancer was developed. Using this technique the investigator identified a particular feature of gastric cancer with family history, multiplicity, and particular histological type.4.Repair genes such as NEIL1 and MYH were altered both in somatic and germline DNA of gastric cancer with/without family history of cancer. Newly identified polymorphism of MYH is shown to be clearly associated localization alteration.5.A novel LKB1 mutation was identified in Peutz-Jeghers syndrome with gastric cancers.6.Eph /EFN family genes were investigated in gastric and colorectal cancers. Germline and somatic mutation searches were performed expecting the situation for familial prostate and familial hyperplastic colorectal polyposis. Loss of heterozygosity of EPHB2 in colorectal cancer was demonstrated, and EPHA2 expression in gastric cancer was documented. EFNA1 suppressed the growth of EFHA2 expressing gastric cancer cell lines. These genes were demonstrated to interact with Tiam1, which is localized in the candidate area of gastric cancer predispostiion according to sib-pair analyses.7.Extension to searches for germline mutations of candidate genes in familial gastric cancer cases.8.A novel polymorphism in KLK12 was found in gastric cancer patients and alteration in gastric cancer was described.

结果：1.日本家族性胃癌患者中存在CDH 1基因的错义突变; 2. OGG 1基因多态性改变了生活方式依赖的上消化道癌发病风险; 3.建立了一种新的胃癌病理档案中染色体不稳定性检测方法。利用该技术，研究者确定了具有家族史、多样性和特定组织学类型的胃癌的特定特征。4.有或无癌症家族史的胃癌的体细胞和生殖细胞DNA中的修复基因如NEIL 1和MYH均发生改变。5.在Peutz-Jeghers综合征合并胃癌患者中发现了一种新的LKB 1突变。6.对Eph/EFN家族基因在胃癌和结直肠癌中的表达进行了研究。进行了生殖系和体细胞突变搜索，以期待家族性前列腺和家族性增生性结直肠息肉病的情况。EPHB 2在结直肠癌中的杂合性缺失被证实，EPHA 2在胃癌中的表达被记录。EFNA 1抑制表达EFHA 2的胃癌细胞系的生长。7.扩展到家族性胃癌病例中候选基因的生殖系突变研究; 8.在胃癌患者中发现KLK 12基因的一个新的多态性，并描述了其在胃癌中的改变。

项目成果

Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.

CYP2C19代谢基因型状态不佳是日本幽门螺杆菌感染患者发生胃癌的危险因素。

• 发表时间: 2005
• 期刊: Aliment Pharmacol Ther. 22
• 作者: Sugimoto M;Sugimura H et al.
• 通讯作者: Sugimura H et al.

Vinies P, Sugimura H et al.: "CYP1A1 T3801 C polymorphism and lung cancer : a pooled analysis of 2451 cases and 3358 controls."Int J Cancer. 104. 650-657 (2003)

Vinies P、Sugimura H 等人：“CYP1A1 T3801 C 多态性与肺癌：2451 例病例和 3358 例对照的汇总分析。”Int J Cancer。

Pilot study of arbitrarily primed PCR-single stranded DNA conformation polymorphism analysis for screening genetic polymorphisms related to specific phenotypes.

任意引物PCR-单链DNA构象多态性分析筛选与特定表型相关的遗传多态性的初步研究。

• 发表时间: 2005
• 期刊: Clin Chim Acta (in press)
• 作者: Maekawa M;Taniguchi T;Uramoto T;Higashi H;Horii T;Takeshita A;Sugimura H;Kanamori M
• 通讯作者: Kanamori M

Amplicons on human chromosome 11q are located in the early/late-switch regions of replication timing

• DOI: 10.1016/j.ygeno.2004.08.001
• 发表时间: 2004-11-01
• 期刊: GENOMICS
• 影响因子: 4.4
• 作者: Watanabe, Y;Ikemura, T;Sugimura, H
• 通讯作者: Sugimura, H

EPHA2/EFNA1 expression in human gastric cancer

• DOI: 10.1111/j.1349-7006.2005.00007.x
• 发表时间: 2005-01-01
• 期刊: CANCER SCIENCE
• 影响因子: 5.7
• 作者: Nakamura, R;Kataoka, H;Sugimura, H
• 通讯作者: Sugimura, H