Abstract

The focus of this project is the use of CYP1A1 gene to monitor human exposure to aromatic hydrocarbons, and to explore the molecular basis of CYP1A1 polymorphisms as cancer susceptibility factors in African Americans. A new quantitative reverse transcriptase PCR method for measurement of gene expression in various indicator tissues (frozen blood, nasal epithelial cells, exfoliated bladder epithelial cells), of people exposed to cigarette smoke, creosote and charcoal broiled foods will be developed and validated. This method, which uses a homologous internal standard (HIS) for accurate quantitation, has the promise of becoming a valuable tool in the development of new biomarkers of exposure based on gene expression in small samples of fresh or stored human tissue. The investigators will extend their research into the mechanisms of individual differences in cancer susceptibility, by investigating the biochemical functional significance of two CYP1A1 restriction polymorphisms that they have found to be linked with cancer risk in African Americans. The investigators will determine whether either of these RFLPs are linked with other polymorphisms in the CP1A1, AHR or ARNT genes in African Americans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES008363-04
Application #
6055960
Study Section
Special Emphasis Panel (ZRG4-ALTX-2 (01))
Project Start
1997-09-01
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2001-08-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Medicine & Dentistry of NJ
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
City
New Brunswick
State
NJ
Country
United States
Zip Code
08903

  Publications

Garte, Seymour; Ganguly, Sabya; Taioli, Emanuela (2003) Effect of genotype on steady-state CYP1A1 gene expression in human peripheral lymphocytes. Biochem Pharmacol 65:441-5
Ford, J G; Li, Y; O'Sullivan, M M et al. (2000) Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans. Carcinogenesis 21:1971-5
Taioli, E; Bradlow, H L; Garbers, S V et al. (1999) Role of estradiol metabolism and CYP1A1 polymorphisms in breast cancer risk. Cancer Detect Prev 23:232-7
Garte, S (1998) The role of ethnicity in cancer susceptibility gene polymorphisms: the example of CYP1A1. Carcinogenesis 19:1329-32
Taioli, E; Ford, J; Trachman, J et al. (1998) Lung cancer risk and CYP1A1 genotype in African Americans. Carcinogenesis 19:813-7
Taioli, E; Zocchetti, C; Garte, S (1998) Models of interaction between metabolic genes and environmental exposure in cancer susceptibility. Environ Health Perspect 106:67-70