To reach the National Cancer Institute's goal of reducing cancer mortality 50% by the year 2000, significant progress will have to be made in the prevention of lung cancer, the leading cause of U.S. cancer mortality among both men and women. The primary prevention strategy has traditionally been a population based effort to reduce cigarette smoking. However, even among individuals with chronic environmental exposures, such as long term cigarette smoking, the risk of lung cancer is relatively low. Preliminary studies suggest that this risk is unevenly distributed, with certain individuals in families having much greater risks of lung cancer development. Such clustering in families suggests that genetic susceptibility may be a factor in carcinogenesis. A more effective prevention strategy could be designed if these individuals could be identified. Previous studies have identified a number of genes that may influence susceptibility to lung cancer. These loci are felt to mediate lung cancer risk through the detoxification of (or failure to detoxify) common environmental agents such as cigarette smoke. The primary goal of this study is to relate lung cancer susceptibility to DNA based variation among two superfamilies of detoxification loci, the P450 and GST families. Joint evaluation of variation of these genes will permit the precise determination of the relative contribution of each locus to lung cancer risk. The genetic profiles will then be used to look for associated changes in etiologic loci (characterized in other components of the application) and differences in family history. The profiles will also be used to investigate whether feedback on genetic constitution influences perception of risk and adherence to public health recommendations among high risk individuals.
