Genetic Polymorphisms and Interindividual Variation in Susceptability to Cancer of the OropharynxEPA Grant Number: R825282
Title: Genetic Polymorphisms and Interindividual Variation in Susceptability to Cancer of the Oropharynx
Investigators: Henner, William D. , McWilliams, Jeffrey E.
Current Investigators: Henner, William D.
Institution: Oregon Health & Sciences University
EPA Project Officer: Reese, David H.
Project Period: October 1, 1996 through September 30, 1999 (Extended to September 30, 2000)
Project Amount: $616,325
RFA: Role of Interindividual Variation in Human Susceptibility to Cancer (1996) RFA Text | Recipients Lists
Research Category: Health Effects , Human Health , Health
Description:Tobacco smoke is known to contain a complex mixture of chemicals, many with the potential for promoting carcinogenesis. Although a large portion of the population uses tobacco, only a small fraction of individuals will develop tobacco-induced malignancies. Our hypothesis is that a substantial portion of the variation in human susceptibility to tobacco-induced cancers is due to the presence of genetic polymorphisms among the exposed population. These polymorphisms, that result in altered function of detoxification enzymes, DNA repair proteins, tumor supressor genes or proto-oncogenes, may alter an individual's susceptibility to carcinogenesis. Previous work by this group and others has implicated DNA polymorphisms in the GSTM1, CYP1A1, and p53 genes as risk factors for development of tobacco-induced carcinoma of the lung.
Another malignancy, squamous cell carcinoma of the mouth, pharynx, and larynx (oropharynx), has an extremely strong epidemiologic link to combined tobacco and ethanol exposure. This research proposes to test the hypothesis that common DNA polymorphisms in detoxification enzymes (GSTM1, GSTT1, NAT1, NAT2, CYP1A1) and proto-oncogenes (p53, H-ras) confer an altered risk for the development of squamous cell carcinoma of the oropharynx. The research will perform a case-control study of 380 cases of squamous cell carcinoma of the oropharynx and 760 controls matched for age, sex, and race. The presence of each of the polymorphisms will be assesed by PCR on DNA isolated from the blood of each study subject. The distribution of each polymorphism among the cases and controls will be determined and odds-ratios for the association of a particular polymorphism with case-control status will be analyzed. These results will allow us to quantify the contribution of these polymorphisms to the risk of developing oropharyngeal cancer. Also, by stratifying our analysis, we will be able to provide better estimates of the frequency of these susceptible alleles in the overall population and in various racial and ethnic groups.