TOBACCO METABOLISM GENES AND GASTRIC CANCER

烟草代谢基因与胃癌

• 批准号: 2896775
• 负责人: ANNA H. WU
• 金额: $ 1.64万
• 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 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2896775
• 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.

在最近完成的胃癌病例对照研究中， 加州烟草相关疾病研究计划3RT-0122），我们 收集了大量关于生活方式因素的问卷数据， 600多名胃癌患者和同等数量的人口 对照 我们的研究结果表明，主动吸烟 增加了胃癌的风险，这与 吸烟与胃癌发生的关系 然而，烟草烟雾诱导胃溃疡的确切机制 人类的癌症仍然不清楚。 越来越多的证据表明 酶系统包括细胞色素P450 CYP 1A 1的遗传多态性 （CYP 1A 1），髓过氧化物酶（MPO）和谷胱甘肽S-转移酶（GST）是 参与烟草致癌物质的代谢并影响 肺癌和膀胱癌的风险。 我们假设这些 多态性基因也在决定吸烟者的吸烟风险方面发挥作用。 胃癌 探讨烟草致癌物代谢的一系列作用 基因影响胃癌风险，我们将使用材料和 胃癌病例对照研究资料 （3RT-0122）。 收集350例胃癌患者的血沉棕黄层 以及450名年龄、性别和种族相匹配的对照人群。 我们正在寻求 支持处理这些血沉棕黄层和DNA提取以及随后的 对提取的DNA进行基因分型测定。 具体来说，我们将测试 胃癌的发病率是多少？ a）具有GSTM 1 null、GSTT 1 null和/或GSTT 1 null的个体， GSTP 1 GG基因型;和B）携带突变的CYP 1A 1等位基因。 我们还将 胃癌的发病率是多少？ MPO基因突变型AA等位基因纯合的个体。我们将 确定这些遗传位点的独立影响及其 相互作用，如果有的话，对胃癌的发展。 在 此外，我们将调查吸烟暴露水平是否会改变 基因与疾病的关系