Genetic polymorphism and susceptibility of common cancer

常见癌症的基因多态性与易感性

• 批准号: 10470056
• 负责人: SUGIMURA Haruko
• 金额: $ 6.85万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470056/
• 关键词: polymorphism; common cancer; stomach; lung; CPY; OGG; IL-1; gastritis; Cyp2E1; Cyp1A1; OGG1; 分子疫学; 肺癌; 胃癌; 症例対照研究; ニトロソアミン; hOGG1; 多型; 80H-グアニン

Rsal polymorphism of CYP2E1, Ser/Cys polymorphism of OGG1, Ile/Val polymorphism of CYP1A1, IL-1b polymorphism were evaluated in lung and gastric cancer case-controls and chronic gastritis with Helicobacter pylori infection. Val homozygotes, Cys homozygotes were related to the increased risk of squamous cell carcinoma of the lung after adjustment of smoking and age. CYP2E1 variant alleles played a protective role against gastric cancer when we adjusted meal consumption. IL-1b polymorphism is highly related with severity of chronic gastritis due to helicobacter pylori infection.A profile of chormosomal Instability of gastric cancer with high familial predisposition was different with that of sporadic gastric cancer.Effects of common environmental carcinogens like benzopyrene were investigated especially on the signaling molecules of pix and eph receptors.These observations together and segregation analysis of Japanese families of gastric cancel suggest existence of genetic predisposition in human common cancers and elucidation of these issues will facilitate a launch of so-called tailor made prevention and medicine.

在肺癌和胃癌病例对照以及幽门螺杆菌感染的慢性胃炎中评估了CYP2E1的Rsal多态性、OGG1的Ser/Cys多态性、CYP1A1的Ile/Val多态性、IL-1b多态性。调整吸烟和年龄后，Val纯合子、Cys纯合子与肺鳞状细胞癌风险增加相关。当我们调整膳食摄入量时，CYP2E1变异等位基因对胃癌发挥了保护作用。 IL-1b多态性与幽门螺杆菌感染引起的慢性胃炎的严重程度密切相关。高家族易感性胃癌的染色体不稳定性特征与散发性胃癌不同。重点研究了苯并芘等常见环境致癌物对pix和eph受体信号分子的影响。 对日本胃癌家族的分离分析表明，人类常见癌症存在遗传易感性，阐明这些问题将有助于推出所谓的量身定制的预防和药物。

项目成果

Kitayama Y,Sugimura H. et al.: "Different Vulnerability among Chromosomes to Numerical Instability In Gastric Carcinogenesis : Stage-dependent analysis by FISH using Microwave Irradiation."Clinical Cancer Research. 6. 3139-46 (2000)

Kitayama Y、Sugimura H. 等人：“胃癌发生过程中染色体对数值不稳定性的不同脆弱性：使用微波辐射进行 FISH 的阶段依赖性分析。”临床癌症研究。

Ying Wang: "Mutational analysis of multiple target genes in histologically heterogeneous gastric cancer with microsatellite instability." Japanese Journal of Cancer Research. 89. 1284-1291 (1998)

Ying Wang：“具有微卫星不稳定性的组织学异质性胃癌的多个靶基因的突变分析。”

Toshifumi Nakamura: "Hepatocellular Carcinoma in Type 1a Glycogen Storage Disease with Identification of a Glucose-6-Phosphatase Gene Mutation in One Family" Journal of Gastroenterology and Hepatology. (in press).

Toshifumi Nakamura：“1a 型糖原累积病中的肝细胞癌与一个家族中葡萄糖 6 磷酸酶基因突变的鉴定”《胃肠病学和肝脏病学杂志》。

Hiroyuki Konno: "Antitumor effect of a neutralizing antibody to vascular endotehlial growth factor on liver metastasis of endocrine neoplasm." Japanese Journal of Cancer Research. 89. 933-939

Hiroyuki Konno：“血管内皮生长因子中和抗体对内分泌肿瘤肝转移的抗肿瘤作用。”

Otsuki Y., Sugimura H. et al.: "Tumor metastasis suppressor nm23-H1 regulates Rac1 GTPase byinteraction with Tiam1"Proceedings National Academy of Science, USA.. 98(8). 4385-90

Otsuki Y.、Sugimura H. 等人：“肿瘤转移抑制因子 nm23-H1 通过与 Tiam1 相互作用调节 Rac1 GTPase”美国国家科学院院刊，98(8)。