PHILADELPHIA - The University of Pennsylvania School of Medicine, in association with Pennsylvania State University Medical College and Lincoln University, has received $4.2 million to study gene-environment interactions that increase the risk of lung cancer in African American and Caucasian smokers and non-smokers. The funds were awarded from Pennsylvania’s share of the national tobacco settlement for 2006-2007.
The award, which was announced by Governor Rendell last month, will fund the establishment of a Center for Gene-Environment Interactions in Lung Cancer directed by Steve Whitehead, PhD, Professor of Pharmacology. The study will be conducted under the Gene-Environment Initiative of Penn’s Center of Excellence in Environmental Toxicology (CEET), directed by Trevor M. Penning, PhD.
Lung cancer is the leading cause of cancer deaths in the adult U.S. population. “This year alone 174,500 new cases of lung cancer will be diagnosed and almost as many deaths will result,” notes Penning. “Eighty-five to ninety percent of all lung cancer is seen in individuals who smoke cigarettes, yet only ten-percent of those who smoke will succumb to the disease. These statistics suggest that a significant gene-environment interaction exists.”
Cigarette smoke contains two major classes of cancer-causing chemicals: those derived from nicotine and those derived from polycyclic aromatic hydrocarbons (PAHs). PAHs are also produced by burning fossil fuels and are ubiquitous environmental pollutants. “PAHs are present in soot that is found at relatively high concentrations in the air we breathe in urban environments,” explains Penning. “Exposure to environmental PAHs may also account for lung-cancer incidence in people who have never smoked.”
The researchers aim to enroll and compare 600 lung-cancer patients from Philadelphia, which has high concentrations of air pollutants, and 600 patients from Hershey, Pa., which has comparatively unpolluted air. In addition, for the 600 recruits in the Philadelphia-based part of the project, the investigators hope to recruit 300 African Americans and the same number of Caucasians to study possible racial differences in gene-environment causes of lung cancer.
Each site will also recruit 600 control individuals who do not have lung cancer, even though they have the same smoking behavior and exposures to pollutants.
The study subjects will answer questions about their smoking history and exposure to airborne pollutants. These pollutants will also be mapped cartographically using GIS technologies to ascertain distribution in each study location.
Exposure to air pollutants for each subject will be analyzed together with their individual variation in approximately 100 genes. “The genes to be tested are considered to be very important for dealing with the carcinogens that are known to cause lung cancer and include many of those responsible for the metabolism and detoxification of carcinogens and for repairing DNA damage caused by carcinogens,” explains Whitehead.
Additionally, current exposure to nicotine and PAHs will be estimated by measuring molecules called biomarkers produced from these chemicals in the body. This is an important component to the study, especially for estimating carcinogen levels in participants who have never smoked but have been exposed to air pollutants.
Whitehead and Penning both note that urban areas that are most polluted are very often occupied by residents of lower socio-economic status and issues of health-disparity and environmental justice exist. Faculty and student interns from Lincoln University will conduct questionnaire-based surveys to identify health-care disparities between the various populations to be enrolled. In addition, they will examine how information about genetic risk is understood and acted upon by the various participating groups.
“Once lung cancer is diagnosed, the five-year survival rate is less than 15 percent,” notes Penning. “This study provides the opportunity to identify those individuals who may be genetically pre-disposed to lung cancer. This genetic information could provide the impetus for high-risk individuals to enter smoking cessation programs. In addition, a better understanding of the relationship between pollution and genetic factors in lung cancer would inform agencies involved in urban planning and facilitate the formulation and implementation of environmental health policies.”
This release can be viewed at www.pennhealth.com/news.
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