Grantee Research Project Results
Interindividual Variations in Genetic Polymorphisms as Risks for Colorectal Cancer
EPA Grant Number: R825280Title: Interindividual Variations in Genetic Polymorphisms as Risks for Colorectal Cancer
Investigators: Lang, Nicholas P. , Ambrosone, Christine , Frame, Lynn , MacLeod, Stewart , Kadlubar, Fred F. , Stotts, Craig
Current Investigators: Lang, Nicholas P. , Ambrosone, Christine , MacLeod, Stewart , Kadlubar, Fred F. , 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: Aja, Hayley
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: Human 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 projectJournal Articles:
Journal Articles have been submitted on this project: View all 10 journal articles for this projectSupplemental Keywords:
genetics, polymorphism, cancer, susceptibility, molecular epidemiology, human, HAA, Health, Risk Assessments, Disease, Disease & Cumulative Effects, cancer risk, carcinogens, enzyme systems, health effects, biological markers, environmental stressors, harmful environmental agents, risk assessment, human exposure, susceptibility, genetic polymorphisms, cancer prevention, immune system effects, cancer risk assessment, environmental toxicant, gene-environment interaction, heterocyclic aromatic amines, exposure assessment, vulnerability, interindividual variationsProgress and Final Reports:
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.