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What does EAGLE Stand for?
Environment And Genetics
in Lung
Cancer Etiology
What is the study design?
EAGLE is a large, multicenter, population–based molecular epidemiology
case-control study of lung cancer with a major biospecimen component
conducted in the Lombardy Region of Italy from 2002-2005.
What is the purpose of the study? Don’t we already know that
smoking causes lung cancer?
The role of smoking has been well-documented in lung cancer for over 50 years. Less well-understood is why only 15-20% of smokers are afflicted with lung cancer and a small proportion of lung cancer occurs in the absence of smoking. A key goal of the study is to understand the role of inherited variation in smokers with lung cancer.
Who are the collaborators in the study?
Maria Teresa Landi
and Neil Caporaso are the co-Principal Investigators (PI) of the study.
Pier Alberto Bertazzi is the head of the coordinating center in Italy,
Angela Pesatori and Dario Consonni play key
roles in management and coordination, and database operations, respectively.
Other key Italian and US collaborators are listed under COLLABORATORS,
elsewhere on this website.
Is it possible to collaborate with the study?
Epidemiologists
or others interested in collaboration should contact either Dr. Landi or
Dr. Caporaso for more information. Collaborations with scientifically and
ethically appropriate investigators are welcomed.
How many subjects participated in EAGLE?
There are over
2000 lung cancer cases and 2000 population-based controls in the study.
When did the study take place?
The study was conceived,
organized and planned by Dr. Landi and Dr. Caporaso in the late 1990’s.
A series of ethical, administrative, and scientific approvals were obtained.
Initial approval of the concept entitled, ‘Genetic
Epidemiology of Lung Cancer and Smoking’ was obtained on September
2, 1999 and a follow-up revision was approved on April 9, 2003 from the
Division of Cancer Epidemiology and Genetics, Senior Advisory Group.
The contract, ‘Genetic Epidemiology of Lung Cancer and Smoking’ was
awarded September 30, 2000 to EPOCA. A pilot study was conducted in 2001
and formal field operations of the study began in April 2002 and concluded
in 2005. Currently, data clean up, database formation,
preparatory laboratory work (i.e. DNA extraction, pilot studies of various
markers) have been completed, and analyses of epidemilogic variables
and genetic markers are ongoing.
What information was collected on EAGLE participants?
Participants
in the study complete 2 large questionnaires. One is a computer-assisted
programmed instrument (CAPI) that includes information on lung cancer
risk factors that include questions on demographics, detailed smoking
history (quitting history, other tobacco use), family history of lung
cancer and other cancers, occupational exposures, environmental tobacco
smoke history, medical history, and residential history.
The second, SELF-ADMINISTERED questionnaire includes questions on personality,
anxiety and depression, attention and ability to focus, diet, meat preparation
method and doneness, alcohol consumption, attitudes about smoking, and
stages of quitting.
Two additional questionnaires including a subgroup of
the questions in the CAPI and Self –administered questionnaires were
administered to next of kin and siblings of the affected individuals if
needed.
A variety of other clinical forms and documentation, i.e, detailing staging,
imaging, clinical laboratory results, pathology reports and others are also
available.
What biospecimens are collected on EAGLE participants?
Subjects
contributed blood (which is divided into various components for storage
including serum, plasma, buffy coat, red blood cells, DNA, RNA, whole
blood, and blood cards) or, in rare occasions, buccal cell samples. Tissue
blocks, tissue
slides, and
fresh tissue (frozen in liquid nitrogen)
were obtained from operative candidates. The proportion of subjects from
whom genetic material is available is close to 100%.
What types of quality control were built into the study?
To
insure integration of process across institutions, at the beginning of
the project we created Standard Operating Procedures (SOPs) and planned
and conducted Quality Assurance/Quality Control visits on a periodic
basis. Weekly conference calls were held throughout the course of the
study to monitor adherence with study procedures and to assess milestones.
A few times a year, in person site visits were conducted where laboratory,
data storage facilities, and hospitals were visited and meetings where
conducted with key personnel. When necessary, special meetings were arranged
to deal with problems, occasionally by video conference. Site visits often
included scientific presentations. Monthly and annual reports were
reviewed. Study progress was also reported to a group of investigators
from the Division of Cancer Epidemiology and Genetics of NCI that assessed
study activity and recommended technical, scientific or management changes
when appropriate. Detailed study manuals covering procedures for Research
Physicians, Laboratory personnel, Data Processing Center staff were in
place.
What are some of the ethical protections in the study?
The
study has undergone formal ethical review and received approval from
Institutional Review Board (IRB) at the National Cancer Institute. The
participating hospitals and the Coordinating Center in Italy also have
formally constituted ethical bodies which have reviewed the study. The
IRB’s in Italy and
in the United States revisit the study on a yearly basis. All study
subjects received a detailed informed consent that they signed in
order to participate. Subjects could refuse to participate in any part
of the study, for example, an individual could elect to complete a questionnaire,
but refuse to contribute any blood. No
tissue was obtained, if it was required for clinical tests. All study
procedures were conducted using standard operating procedures (SOPs)
to maximize patient and staff safety, and to insure the scientific integrity
of the results. Data were stored free of patient identifiers.
Why is the study unique?
EAGLE is one of the largest case-control
studies of lung cancer in the world, with hish response rate in cases
and controls. It is the only case-control study of this size and extensive
biospecimen collection to be population based. The study is integrative,
that is it anticipates testing and combining multiple epidemilogical,
clinical, behavioral, and laboratory-based questions in lung cancer.
What are the future plans for the study?
A variety of descriptive
and technology-based analyses involving lung cancer and smoking are planned.
Collection of information on lung cancer treatment and outcome, quality
of life and survival is planned for late 2006-2007.
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