Lung cancer and Chronic Obstructive Pulmonary Disease (COPD) are two of the most common and most deadly pulmonary diseases. There is no cure for COPD, and it represents the 4th leading cause of death in the United States. Lung cancer is the leading cause of cancer-related deaths in the US, and little improvement has been made in diagnosis or treatment, resulting in a dismal 15% five-year overall survival rate. The most important risk factor for both diseases is cigarette smoking; however, occupational factors and family history are also known to increase risk. Additionally, a personal history of COPD has consistently been shown to increase risk of lung cancer. To identify chromosomal regions that are inherited with disease, several groups have collected DMA from families with multiple affected relatives and performed linkage analyses. In COPD, a region on chromosomes 6q-ter has been associated with lung function and COPD. In lung cancer, a single linkage analysis reported evidence of linkage between a region also on chromosome 6q and lung, laryngeal and pharyngeal cancers. These linkage studies have identified regions of interest and may help future research pinpoint genes that are associated with both lung cancer and COPD. However, these regions are still quite large and encompass hundreds of genes, requiring further research to isolate susceptibility genes. The overall goal of this research plan is to investigate the importance of chromosome 6 on lung cancer and COPD development. We hypothesize that in addition to cigarette smoking, the similarities between COPD and lung cancer development arise from a common genetic pathway(s). We believe that using a variety of statistical techniques and newly available resources, such as the HapMap, will provide novel insight to the etiology of these conditions and potentially identify new targets to improve treatment and survival. This proposal describes a five-year research plan to acquire knowledge and skills to become an independent cancer researcher, with specialized skills in the analysis of genetic data. This project uses existing data and DNA from a case-control study of women with adenocarcinoma of the lung, including those with both lung cancer and COPD, lung cancer only, COPD only, and cancer and COPD-free controls. Additionally, a small number of COPD cases will be prospectively collected. The scope of this project encompasses several disciplines, including epidemiology, genetics, and bioinformatics.