Open Access Highly Accessed Study protocol

Environment And Genetics in Lung cancer Etiology (EAGLE) study: An integrative population-based case-control study of lung cancer

Maria Teresa Landi1*, Dario Consonni2, Melissa Rotunno1, Andrew W Bergen1, Alisa M Goldstein1, Jay H Lubin1, Lynn Goldin1, Michael Alavanja1, Glen Morgan3, Amy F Subar3, Ilona Linnoila4, Fabrizio Previdi2, Massimo Corno2, Maurizia Rubagotti2, Barbara Marinelli2, Benedetta Albetti2, Antonio Colombi2, Margaret Tucker1, Sholom Wacholder1, Angela C Pesatori2, Neil E Caporaso1 and Pier Alberto Bertazzi2

Author Affiliations

1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA

2 EPOCA, Epidemiology Research Center, University of Milan, and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Italy

3 Division of Cancer Control and Population Sciences, National Cancer Institute, NIH, Bethesda, MD, USA

4 Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA

For all author emails, please log on.

BMC Public Health 2008, 8:203  doi:10.1186/1471-2458-8-203

Published: 6 June 2008



Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease.


We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing.


EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.