ACETYLATION AND N-OXIDATION IN COLORECTAL CANCER

一项病例对照研究，检查独立和联合努力， 芳胺乙酰化状态和N-氧化状态和杂环， 芳香胺暴露对结直肠癌发生风险的影响 本文提出 这项赠款申请的具体目的是： 为了证实我们的试点研究的初步结果， 杂环和芳香胺代谢和暴露的假设 饮食或环境中的风险因素。 胺的来源 代谢和暴露作为假定的风险因素， 环境 杂环胺和芳族胺的来源是 研究的是吸烟，饮食和烹饪方法;代谢 待研究的途径包括杂环胺N-氧化状态， O-乙酰化状态。 实验设计涉及芳胺的行为 乙酰转移酶和芳胺N-氧化表型 结肠直肠癌病史和对照组患者。 这 将使用单剂量的咖啡因进行表型分型 作为速溶咖啡饮料服用，并将涉及收集 一个尿液样本。 将测量咖啡因代谢物 通过HPLC和AFMU/1X比值测定表型， 乙酰化和[17 U +17 X]/137 X用于N-氧化。 暴露源将通过使用Willett食品 频率调查问卷将提供总能量的估计 摄入量和微量营养素。 关于具体问题的补充资料 接触胺将收集在一个个人采访，包括 吸烟史、饮食习惯（例如，炭烤，烤或 微波肉类），职业史，医疗和家族史， 基本的人口统计信息。 我们假设，杂环和芳香胺是结肠 对人类的致癌物质。 这些化合物主要存在于煮熟的鱼中 和肉类，也存在于香烟烟雾中。 根据结果， 在我们的初步研究中，我们假设易感性最高的群体 是那些 快速乙酰化和快速N-氧化表型， 高水平的芳胺，例如，红蜂蜜酒煮得很熟。 这项研究应提供有关个人风险的信息， 可以作为试图改变高风险的基础的因素 行为（例如，环境接触和饮食习惯） 患癌症的风险最大 这是一个独特的机会， 实验室科学家和传统科学家之间的合作 流行病学家开发一种新的方法来降低癌症风险 识别.

A case-control study to examine the independent and combined efforts of arylamine acetylator status and N-oxidation status and heterocyclic and aromatic amine exposure on the risk of development of colorectal cancer is proposed. The specific aims of this grant application are: To confirm the initial findings of our pilot study regarding the roles of heterocyclic and aromatic amine metabolism and exposure as putative risk factors from the diet or the environment. The sources amine metabolism and exposure as putative risk factors from the diet or the environment. The sources of heterocyclic and aromatic amines to be studied are cigarette smoking, diet and cooking methods; the metabolic pathways to be studied include heterocyclic amine N-oxidation status and O-acetylation status. The experimental design involves the conduct of arylamine acetyltransferase and arylamine N-oxidation phenotyping on patients with a history of carcinoma of the colorectum and on control patients. This phenotyping will be performed using a single dose of caffeine administered as an instant coffee drink and will involve the collection of a single urine specimen. The caffeine metabolites will be measured by HPLC and the phenotype determined by the radio of AFMU/1X for acetylation and [17U+17X]/137X for N-oxidation. The source of exposure will be determined by the use of the Willett Food Frequency Questionnaire which will provide estimates of total energy intake and micronutrients. Additional information regarding specific exposure to amines will be gathered in a personal interview that covers smoking history, dietary practices (e.g., char-broiled, roasted or microwaved meat), occupational history, medical and family history and basic demographic information. We hypothesize that heterocyclic and aromatic amines are colon carcinogens for humans. These compounds occur primarily in cooked fish and meat and are also present in cigarette smoke. Based on results from our pilot study, we hypothesize that the group at greatest susceptibility for the development of colorectal cancer will be those people who are both rapid acetylation and rapid N-oxidation phenotypes, who are exposed to high levels of arylamines, for example, red mead cooked well done. This study should provide information on relevant individual risk of factors that could serve as a basis for attempts to modify high risk behavior (e.g., environmental exposure and dietary practices) among those at greatest risk to develop cancer. It is a unique opportunity for collaboration between laboratory scientist and traditional epidemiologists in developing a new approach to cancer risk identification.