Interindividual Variations in Genetic Polymorphisms as Risks for Colorectal Cancer

EPA Grant Number: R825280
Title: Interindividual Variations in Genetic Polymorphisms as Risks for Colorectal Cancer
Investigators: Lang, Nicholas P. , Ambrosone, Christine , Frame, Lynn , Kadlubar, Fred F. , MacLeod, Stewart , Stotts, Craig
Current Investigators: Lang, Nicholas P. , Ambrosone, Christine , Kadlubar, Fred F. , MacLeod, Stewart , Stotts, Craig
Institution: University of Arkansas for Medical Sciences , National Center for Toxicology Research
Current Institution: University of Arkansas for Medical Sciences
EPA Project Officer: Reese, David H.
Project Period: November 15, 1996 through November 14, 1999
Project Amount: $538,785
RFA: Role of Interindividual Variation in Human Susceptibility to Cancer (1996) RFA Text |  Recipients Lists
Research Category: Health Effects , Human Health , Health

Description:

Recent evidence has demonstrated that predictions of cancer risk must take into account not only carcinogen exposure but also interindividual variations in the ability to activate or detoxify specific carcinogens. This project is a case-control study of risk associated with various genotypes and exposures in the development of colorectal cancer. Two objectives will be investigated: (1) whether interindividual differences in susceptibility to colon cancer are related to genetically based differences in the polymorphic enzymes responsible for the activation and detoxification of heterocyclic aromatic amines and bicyclic aromatic amines (found in cooked foods, tobacco smoke, and several environmental sources), and (2) whether genotyping provides additional and/or better data that indicate a quantitative relationship between polymorphisms and the risk for colorectal cancer development in those patients for whom phenotyping and environmental exposure data already exists. PCR-based assays will be used to determine the genotype of study subjects for specific polymorphisms that have been linked to the activation or detoxification of these carcinogenic amines. These data will be combined with phenotype data and environmental exposure data for the same study subjects. It is expected that interindividual differences in susceptibility to colorectal cancer will be determined by both the level of exposure to potentially carcinogenic amines as well as by differences in the ability to metabolize these carcinogens. The results will facilitate the identification of individuals who are at increased risk for colorectal cancer due to genetically based differences in their ability to metabolize potentially carcinogenic amines, thus setting the stage for developing better health policies and more accurate exposure limits for these compounds.

Publications and Presentations:

Publications have been submitted on this project: View all 24 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 10 journal articles for this project

Supplemental Keywords:

genetics, polymorphism, cancer, susceptibility, molecular epidemiology, human, HAA, Health, Disease, Risk Assessments, Disease & Cumulative Effects, cancer risk, health effects, risk assessment, immune system effects, vulnerability, interindividual variations, colorectal cancer, gene-environment interaction, enzyme systems, human exposure, carcinogens, susceptibility, genetic polymorphisms, environmental stressors, environmental toxicant, harmful environmental agents, cancer prevention, cancer risk assessment, biological markers, exposure assessment

Progress and Final Reports:

Final Report