In the United States, nearly three-quarters of the oral cancer cases are attributable to tobacco and/or alcohol consumption. Oral carcinogens derived from these exposures include N-nitrosamines, polycyclic aromatic hydrocarbons, aromatic amines, heterocyclic amines, and acetaldehyde that are activated and detoxified by enzyme systems in vivo to intermediates with high and low propensity, respectively, to bind covalently to DNA. Growing evidence indicates that inter-individual variation in the activity of many of these enzyme systems is at least in part under genetic control. In this proposed population-based case-control study, the investigators will test the hypothesis that oral cancer risk is associated with polymorphisms in the genes for enzymes that contribute to an individual's ability to activate and/or detoxify tobacco carcinogens. The specific enzymes (genes) of interest are glutathione-S-transferase M1 (GST-M1) glutathione-S-transferase P1 (SST-P1), microsomal epoxide hydrolase (EPHX), cytochrome p450 2E1 (CYP2E1), alcohol dehydrogenase type 3 (ADH3), N-acetyltransferase types 1 and 2 (NAT1, NAT2), and NAD(P)H:quinone oxidoreductase (NQ01). Cases will be 345 18-65 year-old western Washington male and female residents diagnosed with a first oral cancer between 1985 and 1994; controls will be 526 18-65 year-old residents of the same geographic area selected through random digit telephone dialing and frequency matched on age and gender. All cases and controls have been recruited into two oral cancer case-control studies during which the investigators obtained: (1) in-person interviews eliciting extensive tobacco and alcohol consumption histories, and other risk factor information, and (2) a sample of exfoliated oral tissue from which genomic DNA has been extracted and stored for the majority of subjects. During the proposed activity, they will extract DNA from oral tissue of remaining subjects and conduct molecular analyses on DNA specimens to determine the presence of putative high risk genotypes for the genes of interest. Cases and controls will be compared with respect to the frequency of DNA variants, both overall and among sub-groups likely to vary in exposure to carcinogens (e.g., heavy vs. light smokers). The investigators state that the results of this study will contribute to accumulating knowledge regarding the role of genetic susceptibility to environmental carcinogens in determining cancer risk. They further note that in the future such information could provide the basis for both enhanced individual risk assessment, as well as targeted behavioral interventions to reduce exposures among individuals at particularly high risk of developing tobacco and alcohol-related cancers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012609-03
Application #
6176054
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Sandberg, Ann
Project Start
1998-09-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$322,514
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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