GENE-ENVIRONMENT EFFECTS AND COLON ADENOMAS

描述：（改编自申请人的摘要）。 长期目标是 该应用程序旨在调查环境暴露的影响 结合遗传性宿主因素对常见癌症的风险。 的 项目将利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：肉类、 十字花科蔬菜和阿司匹林。 高肉类饮食被认为 风险因素，而十字花科蔬菜和阿司匹林被认为是 保护性的。 要分析的遗传因素是以下变体： N-乙酰转移酶（NAT，代谢肉类致癌物）； 4种不同 谷胱甘肽转移酶（GST，可清除体内发现的抗癌物质） 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 个不同的基因。 该项目将使用来自一个研究中心的受试者（1,000 个病例和 1,000 个对照） 正在进行的研究题为“基于乙状结肠镜检查的息肉病例对照研究”。 受试者是从 2 个乙状结肠镜筛查诊所招募的 洛杉矶凯撒医疗机构医疗中心。 病例无症状 首次诊断出至少 1 个结直肠腺瘤。 控制措施是 选自无腺瘤的受试者。 数据收集自 自填式饮食问卷、面对面访谈 非饮食危险因素、空腹血样和病理报告。 该项目将表征 NAT1、NAT2、GSTM1 的多态性基因， 所有受试者的 GSTM3、GSTT1、PGHS-1、PGHS-2 和 cPLA2。 PCR 检测， 异源双链体分析、DNA 测序和基因表达测定将 用于对基因进行分子表征。 完成分子 分析的目的是提供有关风险机制的信息 肉类和十字花科蔬菜的保护机制 阿司匹林。

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.