GENE-ENVIRONMENT EFFECTS AND COLON ADENOMAS

描述：（改编自申请人摘要）。 的长期目标 本申请旨在研究环境暴露的影响 与遗传宿主因素相结合，对常见癌症的风险。 的 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 保护性的 要分析的遗传因素是以下变量： N-乙酰转移酶（NAT，代谢肉类致癌物）; 4种不同的 谷胱甘肽转移酶（GST），可以清除抗癌剂， 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（cPLA 2，其变体可以模拟磷脂酶A2的活性）。 阿司匹林效应）。 将分析总共9种不同的基因。 该项目将使用受试者（1,000例病例和1,000例对照）， 正在进行的一项名为“乙状结肠镜检查息肉的病例对照研究”的研究。" 受试者已从2个乙状结肠镜检查筛查诊所招募， 位于洛杉矶的凯撒医疗中心。 病例均无症状 首次诊断为至少1个结直肠腺瘤。 对照 选自无腺瘤的受试者。 数据收集自 自我管理的饮食问卷，一个人的采访， 非饮食风险因素，空腹血样和病理报告。 该项目将表征NAT 1、NAT 2、GSTM 1、 所有受试者中的GSTM 3、GSTT 1、PGHS-1、PGHS-2和cPLA 2。 PCR分析， 异源双链分析、DNA测序和基因表达测定将被 用来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， 肉和保护机制，由于十字花科蔬菜， 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.