TOBACCO METABOLISM GENES AND GASTRIC CANCER

烟草代谢基因与胃癌

• 批准号: 2802496
• 负责人: ANNA H. WU
• 金额: $ 8.03万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2802496
• 关键词: cancer risk; chemical carcinogenesis; clinical research; cytochrome P450; drug metabolism; gene environment interaction; gene interaction; genetic polymorphism; genetic susceptibility; genotype; human data; human genetic material tag; linkage mapping; neoplasm /cancer epidemiology; neoplasm /cancer genetics; questionnaires; smoking; stomach neoplasms; tobacco

In a recently completed case-control study of gastric cancer funded by the California Tobacco-Related Disease Research Program 3RT-0122), we have collected extensive questionnaire data on lifestyle factors from over 600 gastric cancers patients and an equal number of population controls. Our results showed that active smoking significantly increased the risk of gastric cancer, consistent with the conclusion of several recent reviews on smoking and gastric cancer development. However, the precise mechanism by which tobacco smoke induces gastric cancer in humans is still unclear. There is increasing evidence that genetic polymorphisms in enzyme systems including cytochrome P450 CYP1A1 (CYP1A1), myloperoxidase (MPO) and glutathione S-transferases (GSTs) are involved in the metabolism of tobacco carcinogens and influence the risks of lung and bladder cancers. We hypothesize that these polymorphic genes also play a role in determining a smokers' risk of gastric cancer. To investigate the roles of a series of tobacco-carcinogen-metabolizing genes in influencing gastric cancer risk, we will use materials and information collected from our case-control study on gastric cancer (3RT-0122). Buffy coats were collected from 350 gastric cancer cases and 450 age-, sex- and race-matched population controls. We are seeking support to process these buffy coats and DNA extraction and subsequent genotyping assays on extracted DNA. Specifically, we will test the hypotheses that the risk of gastric cancer is increased among individuals who: a) possess the GSTM1 null, the GSTT1 null and/or the GSTP1 GG genotypes; and b) carry mutant CYP1A1 alleles. We will also test the hypothesis that risk of gastric cancer is decreased among individuals homozygous for the mutant AA allele of the MPO gene. We will determine the independent effects of these genetic loci and their interactive effects, if any, on gastric cancer development. In addition, we will investigate if the level of smoking exposure modifies any of these gene-disease relationships.

在最近完成的胃癌的病例对照研究中 加利福尼亚烟草相关疾病研究计划3RT-0122），我们 从 超过600名胃癌患者和同等数量的人口 控件。 我们的结果表明，活跃的吸烟显着 增加了胃癌的风险，与结论一致 最近关于吸烟和胃癌发展的评论。 但是，烟草烟雾诱发胃的确切机制 人类的癌症仍不清楚。 有越来越多的证据表明 包括细胞色素P450 CYP1A1在内的酶系统中的遗传多态性 （CYP1A1），霉菌性氧化酶（MPO）和谷胱甘肽S-转移酶（GSTS）是 参与烟草致癌的代谢，并影响 肺和膀胱癌的风险。 我们假设这些 多态基因在确定吸烟者的风险方面也发挥作用 胃癌。 调查一系列烟霉菌原代谢的作用 影响胃癌风险的基因，我们将使用材料和 从我们的胃癌病例对照研究中收集的信息 （3RT-0122）。 从350例胃癌病例中收集Buffy毛衣 以及450岁，性别和种族匹配的人口控制。 我们正在寻找 支持处理这些Buffy外套和DNA提取以及随后的 提取的DNA上的基因分型测定。 具体来说，我们将测试 假设胃癌的风险增加 个人：a）拥有GSTM1空，GSTT1 null和/或 GSTP1 GG基因型； b）携带突变的CYP1A1等位基因。 我们也会 检验以下假设，即胃癌风险降低了 MPO基因的突变体AA等位基因的纯合子。我们将 确定这些遗传基因座的独立影响及其 互动效果（如果有的话）对胃癌发展。 在 此外，我们将调查吸烟水平是否改变 这些基因 - 疾病关系中的任何一个。