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.

上述期间获得以下结果：1.日本家族性胃癌受试者中CDH1的错义种系突变。2.研究者阐明OGG1多态性改变了上消化道癌的生活方式依赖性风险。3.一种新的方法建立了检测胃癌病理档案中染色体不稳定性的方法。利用这项技术，研究人员确定了胃癌的一个特定特征，包括家族史、多重性和特定的组织学类型。4.修复基因，如 NEIL1 和 MYH，在有/无癌症家族史的胃癌体细胞和种系 DNA 中均发生改变。 。新发现的MYH多态性与定位改变明显相关。5.在胃癌Peutz-Jeghers综合征中发现了一种新的LKB1突变。6.在胃癌和结直肠癌中研究了Eph/EFN家族基因。进行种系和体细胞突变搜索，以预测家族性前列腺和家族性增生性结直肠息肉病的情况。证明了结直肠癌中 EPHB2 杂合性的丧失，并记录了胃癌中 EPHA2 的表达。 EFNA1 抑制表达 EFHA2 的胃癌细胞系的生长。这些基因被证明与 Tiam1 相互作用，根据同胞对分析，Tiam1 位于胃癌易感的候选区域。 7. 扩展到家族性胃癌病例中候选基因种系突变的搜索。 8. 一种新的多态性在胃癌患者中发现了 KLK12，并描述了胃癌的改变。

项目成果

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。

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

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

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

Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation

• DOI: 10.1038/sj.emboj.7600486
• 发表时间: 2005-01-12
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Uchida, CH;Miwa, SC;Sugimura, H
• 通讯作者: Sugimura, H