Environment and genetics in lung cancer etiology (EAGLE): a novel population-based case-control study of lung cancer

EAGLE is a large population-based case-control study designed to investigate the genetic and environmental determinants of lung cancer, smoking persistence, survival and therapy efficacy through combined analysis of genetic, environmental, clinical, and behavioral data. Field activities have recently concluded. 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 participation rate was high, 85% in cases and 73% in controls. The study includes 2,117 incident lung cancer cases, both males (78%) and females (22%) of Italian nationality, ages 35 to 79 years old, with verified lung cancer of any histological type, and 2,120 healthy population-based controls matched to cases by age, gender, and residence. Adenocarcinoma was the most frequent histology subtype overall (38%) and in never smokers (62%), and differed by sex (50% in females and 35% in males, overall). Interestingly, bronchoalveolar carcinoma showed the highest frequency in former smokers (53%) compared to current smokers (26%) and never smokers (21%). In contrast, all other histological subtypes, particularly small cell and large cell, had higher frequency in current smokers. Stage I tumors were more frequent in former (49%) than current (43%) smokers, while later stages were more frequent in current smokers. We collected extensive epidemiological, behavioral, and clinical data, as well as multiple biospecimens from virtually all lung cancer cases and controls. Tissue specimens, including multiple fresh “normal” lung tissue and tumor samples, were collected from surgical cases. As expected, tobacco smoking was associated with lung cancer (OR=5.0, 95% CI=4.0-6.1, and OR=11.0, 95% CI=8.8-13.6, in former and current smokers, respectively, when compared with never smokers and adjusting for matching variables). Initial analyses show that family history of cancer in first-degree relatives (OR=1.3, 95% CI=1.1-1.4), and low education level (p=0.003, test for trend, from elementary to post-graduate education) are risk factors for lung cancer in EAGLE, even after adjustment for smoking and matching variables. We are exploring the role of passive smoking, sex, occupation, diet, willingness to participate in the study, and other factors in the association with lung cancer, and behavioral data (Fagerstrom index, measures of depression, anxiety, and personality) in relation to smoking persistence. Extensive genetic investigations are also underway. This study will help answer many questions related to lung cancer etiology.