EAGLE (Environment and Genetics in Lung Cancer Etiology) is a large population-based case-control study designed and conducted to investigate the determinants of lung cancer and smoking persistence using an integrative approach that allows combined analysis of genetic, environmental, clinical, and behavioral data. The study includes over 2,000 incident lung cancer cases, both males and females of Italian nationality, ages 35 to 79 years old, with verified lung cancer of any histological type, and over 2,000 healthy population-based controls matched to cases by age, gender, and residence. NCI investigators recently used data from EAGLE to explore the impact of common genetic variation in inflammatory genes on lung cancer risk in smokers using a genome-wide association study (GWAS). A susceptibility locus for squamous cell lung carcinoma was identified at 12p13.33 (RAD52, rs6489769). Future plans include analyses of tumor genetic alterations and their integration with GWAS data.