Susceptibility to tobacco and alcohol carcinogenesis in the development of aerodigestive tract cancer may be genetically determined. However, few studies have evaluated the interaction of genetic and environmental exposures in risk of cancer. The proposed research will be a case- control study of 10 patients registered at UT M.D. Anderson Cancer Center with previously untreated upper aerodigestive tract cancers and 100 age- and sex-matched peer controls. Environmental exposures will be ascertained from self-administered risk factor questionnaires, and follow-up verification interview. Mutagen sensitivity will be quantitatively assessed by the frequency of chromatid breaks in primary lymphocyte cultures incubated with the radiomimetic clastogen, bleomycin. Chromosome sensitivity will be evaluated as a risk factor for these cancers in univariate matched analysis. Differential sensitivity by location of the primary tumor will be compared. The presence of effect modification between chromosome sensitivity and tobacco ad alcohol use will be assessed. The results of the proposed study will provide a basis for extended research into the biologic significance of chromosome sensitivity and its predictive value in defining individual susceptibility to environmental mutagens. Since patients with aerodigestive tract cancers incur high risks of subsequent primary malignancies, this may also assist in defining patients most at risk for multiple neoplasms.
