The Pittsburgh Center Institute proposes to organize a SPORE for lung cancer (PCI-LCS) with the overall objective of devising effective strategies for preventing the development of lung cancer and for the treatment of patients after diagnosis of this very common and malignant disease. The proposed research projects are closely interconnected and involve a wide array of basic and clinical expertise, that is being focused on lung cancer. Projects are directed towards elucidating the molecular pathogenesis of this disease and identifying and evaluating biological markers that help to define high risk. Project 2 is focused on a detailed assessment of the whole body and local pulmonary activity of the isoenzymes of the cytochrome P450 system, to understand the genetic heterogeneity in susceptibility to environmental carcinogens and to identify additional biomarkers for risk of lung cancer. Project 3 is an epidemiologic study of heavy smokers at high risk of lung cancer, with a focus on assessment of serum oncoproteins as risk factors. Project 4 is a closely linked case control study of some of the high risk individuals, involving bronchoscopy to obtain HBE for detailed studies of differentiation markers and of P450 enzyme profiles.