GENE-ENVIRONMENT EFFECTS AND COLON ADENOMAS

基因环境影响和结肠腺瘤

• 批准号: 2008792
• 负责人: HENRY J LIN
• 金额: $ 10.98万
• 依托单位: LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-15 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2008792
• 关键词: Cruciferae; acyltransferase; adenomatous polyps; aspirin; cancer risk; clinical research; colon polyp; gene environment interaction; genetic polymorphism; glutathione transferase; human subject; isozymes; meat; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition aspect of cancer; prostaglandin endoperoxide synthase; Cruciferae; acyltransferase; adenomatous polyps; aspirin; cancer risk; clinical research; colon polyp; gene environment interaction; genetic polymorphism; glutathione transferase; human subject; isozymes; meat; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition aspect of cancer; prostaglandin endoperoxide synthase

DESCRIPTION: (Adapted from Applicant's Abstract). The long term goal of this application is to investigate effects of environmental exposures combined with heritable host factors on the risk for common cancers. The project will use epidemiology and molecular genetics and will focus on colon adenomas. Environmental exposures to be analyzed include: meat, cruciferous vegetables, and aspirin. High meat diets are believed to be risk factors, whereas cruciferous vegetables and aspirin are believed to be protective. Hereditary factors to be analyzed are variants of: N-acetyltransferases (NATs, which metabolize meat carcinogens); 4 different glutathione transferases (GSTs, which may clear anticarcinogens found in cruciferous vegetables), and the prostaglandin G/H synthetases (PGGS/PGHS) and cytosolic phospholipase A2 (cPLA2, variants of which may mimic the aspirin effect). A total of 9 different genes will be analyzed. The project will use subjects (1,000 cases and 1,000 controls) from an ongoing study titled, "A sigmoidoscopy-based case-control study of polyps." Subjects have been recruited from 2 sigmoidoscopy screening clinics at Kaiser Permanente Medical Centers in Los Angeles. Cases were asymptomatic with a first time diagnosis of at least 1 colorectal adenoma. Controls were selected from subjects free of adenomas. Data were collected from a self-administered dietary questionnaire, an in-person interview of non-dietary risk factors, a fasting blood sample, and pathology reports. The project will characterize polymorphic genes for NAT1, NAT2, GSTM1, GSTM3, GSTT1, PGHS-1, PGHS-2, and cPLA2 in all subjects. PCR assays, heteroduplex analysis, DNA sequencing, and gene expression assays will be used to molecularly characterize genes. Completion of the molecular analyses is intended to provide information on the mechanism of risk due to meat and the mechanisms of protection due to cruciferous vegetables and aspirin.

描述：（改编自申请人的摘要）。 长期目标的 该应用是为了调查环境暴露的影响 结合可遗传的宿主因素，即常见癌症的风险。 这 项目将使用流行病学和分子遗传学，并将重点放在结肠上 腺瘤。 要分析的环境暴露包括：肉， 十字花科蔬菜和阿司匹林。 据信高肉饮食是 危险因素，而十字花科蔬菜和阿司匹林被认为是 保护的。 遗传因素要分析是： N-乙酰转移酶（NATS，代谢肉类致癌物）； 4不同 谷胱甘肽转移酶（GSTS，可以清除在 十字花科蔬菜）和前列腺素G/H合成酶（PGGS/PGHS） 和胞质磷脂酶A2（CPLA2，其变体可能模仿 阿司匹林效应）。 总共将分析9种不同的基因。 该项目将使用主题（1,000例和1,000个对照） 正在进行的研究标题为“基于乙状结肠镜检查的息肉病例对照研究”。 受试者是从2个sigmoidsocecopy筛查诊所招募的 洛杉矶的Kaiser Permanente医疗中心。 病例无症状 首次诊断至少1个结直肠腺瘤。 控件是 从没有腺瘤的受试者中选择。 数据是从一个 自我管理的饮食问卷，一次面对面的访谈 非肤色危险因素，禁食样本和病理报告。 该项目将表征NAT1，NAT2，GSTM1， 在所有受试者中，GSTM3，GSTT1，PGHS-1，PGHS-2和CPLA2。 PCR分析， 杂化分析，DNA测序和基因表达测定将是 用于分子表征基因。 分子的完成 分析旨在提供有关由于 肉和由于十字花科蔬菜而引起的保护机制 阿司匹林。