GENE-ENVIRONMENT EFFECTS AND COLON ADENOMAS

描述：(改编自申请人摘要)。的长期目标是 此应用程序用于调查环境暴露的影响 结合可遗传宿主因素对常见癌症的风险。这个 该项目将使用流行病学和分子遗传学，并将重点放在结肠 腺瘤。待分析的环境暴露包括：肉类， 十字花科蔬菜和阿司匹林。高肉类饮食被认为是 风险因素，而十字花科蔬菜和阿司匹林被认为是 防护性的。要分析的遗传因素有以下几种： N-乙酰转移酶(NAT，代谢肉类致癌物质)；4种不同 谷胱甘肽转移酶(GSTs)，可清除在 和前列腺素G/H合成酶(PGGS/PGHS)。 和胞浆磷脂酶A2(CPLA2)，其变体可模拟 阿司匹林效应)。共有9个不同的基因将被分析。 该项目将使用来自 正在进行的研究名为“一项基于乙状结肠镜检查的息肉病例对照研究”。 受试者是从2个乙状结肠镜检查诊所招募的，地址是 洛杉矶的凯撒永久医疗中心。2例无症状 首次诊断至少1例结直肠腺瘤。对照组为 选自无腺瘤的受试者。数据是从一个 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、 所有受试者的GSTM3、GSTT1、PGHS-1、PGHS-2和cPLA2。聚合酶链反应检测， 异源双链分析、DNA测序和基因表达分析将 用来确定基因的分子特征。分子的完成 分析旨在提供有关以下原因导致的风险机制的信息 十字花科蔬菜对肉类的保护作用机制 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.