EAGLE is a large population-based case-control study designed and conducted to investigate the genetic and environmental 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. The participation rate was high: 85% and 73% in cases and controls, respectively.

Lung cancer cases were enrolled from 13 hospitals within the Lombardy region of Italy. The healthy controls were randomly selected from the same residential area of the lung cancer cases. The study setting, the Lombardy region of Italy, is served by a network of modern hospitals, medical schools, and a regional health service. Within the Lombardy region, the catchment's area includes 5 cities and 216 surrounding municipalities, encompassing, in the selected age range, over 1.3 million people.

Extensive epidemiological data have been collected through both an interview-based computer-assisted questionnaire and a self-administered questionnaire. Available data includes demographical characteristics, detailed smoking history (active and passive), family history of lung cancer and other cancers, previous lung diseases, medications, diet, alcohol, attempts at quitting smoking, anxiety, depression, personality scores, occupation, reproductive and residential history.

Clinical data (stage, grade, histology, imaging and pathology reports, spirometry, and routine laboratory studies) are recorded. All study subjects donated a blood sample (or, rarely, a buccal rinse sample), which was processed to obtain cryopreserved lymphocytes, RBC, granulocytes, DNA, RNA, whole blood, buffy coat, serum, plasma, and blood cards. Lung tissue paraffin blocks and slides were collected from the cases who underwent surgery, biopsy or cytological examination of the lung tumor. Multiple fresh “normal” lung tissue and tumor samples, frozen in liquid nitrogen within 20 minutes of excision, were also collected from over 500 surgical cases.

All data and biospecimen information are stored in a secure relational database. Quality control procedures have been implemented to ensure accuracy, completeness, and privacy of the data collected. Genetic and epidemiological studies are ongoing. This study will help answer many questions related to lung cancer etiology in the near future.