Role of Interindividual Variation in Human Susceptibility to Cancer Toxicological Implications of a Polymorphism in NQO1

EPA Grant Number: R825281
Title: Role of Interindividual Variation in Human Susceptibility to Cancer Toxicological Implications of a Polymorphism in NQO1
Investigators: Ross, David
Institution: University of Colorado Health Sciences Center
EPA Project Officer: Hahn, Intaek
Project Period: December 15, 1996 through December 14, 1999
Project Amount: $531,787
RFA: Role of Interindividual Variation in Human Susceptibility to Cancer (1996) RFA Text |  Recipients Lists
Research Category: Health Effects , Health

Description:

NAD(P)H:Quinone oxidoreductase (NQO1, DT-diaphorase, EC 1.6.99.2) is an important enzyme with respect to the detoxification of xenobiotics and has been proposed to be important in both chemoprotection and chemoprevention. A polymorphism in NQO1 has recently been characterized which results in an absence of NQO1 protein and activity. The focus of this study will be to examine whether the polymorphism has any relevance for chemoprotection and chemoprevention. The prevalence of the NQO1 polymorphism will be characterized in different ethnic groups. Whether this polymorphism is associated with an increased incidence of benzene-induced DNA damage and hematotoxicity in occupationally-exposed workers will also be examined. A role for NQO1 in protection against cancer has been proposed and whether there is an increased prevalence of the NQO1 polymorphism in individuals who are genetically predisposed to colorectal cancer will be determined. The proposed studies should define the role of NQO1 in protection from benzene-induced toxicity and characterize the role of NQO1 in genetic predisposition to colorectal cancer.

Supplemental Keywords:

genetics, polymorphism, cancer, susceptibility, molecular epidemiology, human, gender, ethnic group, benzene, quinones., RFA, Health, Scientific Discipline, Toxics, Genetics, HAPS, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, genetic susceptability, 33/50, health effects, interindividual variability, molecular epidemiology, polymorphism, carcinogenesis, colorectal cancer, DNA damage, health risks, xenobiotics, ethnic, genetic predisposition, benzene, benzene exposure, benzene induced DNA damage, cancer risks, human exposure, susceptibility, genetic polymorphisms, harmful environmental agents, Benzene (including benzene from gasoline), exposure assessment, genetic diversity, xenobiotic metabolism

Progress and Final Reports:

  • 1997
  • 1998
  • Final