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.

在最近完成的一项关于胃癌的病例对照研究中， 加州烟草相关疾病研究计划3RT-0122) 收集了大量关于生活方式因素的问卷数据，来自 600多名胃癌患者和同等数量的人口 控制。我们的结果显示，主动吸烟显著地 增加患胃癌的风险，这与以下结论一致 最近几篇关于吸烟与胃癌发展的综述。 然而，烟草烟雾导致胃病的确切机制 人类中的癌症仍不清楚。越来越多的证据表明 细胞色素P450、细胞色素P1A1等酶系统的遗传多态性 细胞色素P1A1、髓过氧化物酶和谷胱甘肽S转移酶 参与烟草致癌物的新陈代谢并影响 肺癌和膀胱癌的风险。我们假设这些 多态基因也在决定吸烟者罹患癌症的风险中发挥作用。 胃癌。 探讨一系列烟草致癌物质代谢的作用 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收集的信息 (3RT-0122)。收集了350例胃癌患者的黄褐色大衣 以及450个年龄、性别和种族匹配的人口控制。我们正在寻找 支持处理这些黄褐色大衣和DNA提取以及后续 对提取的DNA进行基因分型。具体地说，我们将测试 假设胃癌的风险在以下情况下增加 个人：a)拥有GSTM1空值、GSTT1空值和/或 GSTP1、GG等位基因；b)携带突变的CYP1A1等位基因。我们还将 检验以下假设：患胃癌的风险降低 MPO基因突变AA等位基因纯合的个体。我们会 确定这些遗传基因座及其各自的独立效应 如果有的话，对胃癌发展的交互作用。在……里面 此外，我们将调查吸烟暴露水平是否会改变 这些基因-疾病关系中的任何一种。