ACETYLATION AND N-OXIDATION IN COLORECTAL CANCER

一项病例对照研究，以检查独立和联合的努力

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.