The overarching strategic plan of this SPORE is to develop methods for identifying persons at greatest risk for developing lung cancer and then preventing this progression. A second, related component is to understand the "cancer gene anatomy" required for lung cancer development and then using this information for early detection, prevention, and the selection and/or development of new rational treatments. We have chosen to invest in three central translational research themes: early detection of genetic alterations coupled with chemoprevention in former smokers; identification of persons with an increased inherited risk of developing lung cancer; and developing new methods of smoking cessation by elucidating genetic contributions to nicotine addiction. To achieve these goals our SPORE has assembled clinicians and. basic scientists including medical oncologists, thoracic surgeons, pulmonary physicians, pathologists, molecular geneticists, molecular and cell biologists, epidemiologists, behavioral and psycho-pharmacologists, biostatisticians, and experts in development of new technologies and informatics. The SPORE, brings together two major complementary strengths in lung cancer research involving UT Southwestern Medical Center (UTSW) and M.D. Anderson Cancer Center (UTMDA) in the areas of molecular pathogenesis, genetic epidemiology, early detection, chemoprevention, and smoking cessation/nicotine addiction. This SPORE consists of 5 inter-related projects and 3 supporting Cores. The projects are: I. Gene-Discovery: Identification of 3p Recessive Oncogenes; 2. Genetic Susceptibility; 3. Molecular Early Detection; 4. Chemoprevention in Former Smokers; and 5. Smoking Cessation and the Genetics of Nicotine Addiction. The Cores are: Administrative (A); Pathology and Tissue Resources (B); and Biostatistics/Informatics (C). All of the scientific projects are: translational in nature; focus on human lung cancer; arose out of conjoint planning between UTSW and UTMDA and involve scientists from both institutions as Co-investigators; interact with the other projects; include basic and clinical investigators; and utilize Core resources. Innovative Developmental and Career Development Projects include new methods for gene discovery and therapeutics development. Achievement of the aims and objectives of this proposal will result in a major decrease in the incidence, morbidity and mortality of lung cancer.