PHILADELPHIA -- The Center of Excellence in Environmental Toxicology (CEET) at the University of Pennsylvania School of Medicine has been awarded $2.3 million over the next four years to study biological indicators of exposure to cigarette smoke. The grant is part of the National Institutes of Health new Genes, Environment, and Health Initiative (GEI). The GEI represents a unique collaboration between geneticists and environmental health scientists. In this first round of awards genetic studies were funded by the National Human Genome Research Institute and biomarker studies were funded by the National Institute of Environmental Health Sciences.
Exposure to tobacco smoke - both mainstream and second-hand - is a leading cause of death in the United States. Cigarette smoke contains about 3,800 chemical constituents, including polycyclic aromatic hydrocarbons (PAHs), which can cause lung, skin, and bladder cancer. What's more, tobacco smoke is associated with cardiovascular disease, chronic obstructive pulmonary disease, and pancreatic disease, and is likely responsible for more deaths than any other environmental exposure.
"Only one in ten smokers get lung cancer, but the five-year survival rate after diagnosis is only 15 percent," says Trevor M. Penning, PhD, CEET's director. "The question is, how can we intervene earlier to identify people most at risk. We aim to look at the interaction of genetic susceptibility to lung cancer and biomarkers of exposure to cigarette smoke. At the end of the day, if we study genetics and exposure together, we'll hopefully have a very strong statement to say who is most at risk."
"This could be like measuring cholesterol for preventing heart disease," says principal investigator Ian Blair, PhD, Professor and Vice Chair of the Department of Pharmacology. "If, for example, a certain chemical change is seen in a smoker's DNA, it might inspire them to give up smoking. You could show them a biomarker panel and say, 'Here's your DNA on smoking and here's DNA without smoking.' This is my vision." Blair is also the Director of Penn's Center for Cancer Pharmacology.
The researchers propose to screen smokers, non-smokers and those regularly in contact with second-hand smoke for a variety of biochemical markers. Previous studies have shown that chemical changes arise within the body, from the tissue level down to the DNA level in people who smoke or who have been exposed to smoke, but this association has never been studied on a large scale with reliable biomarkers.
The plan is to develop a panel of biochemicals, or biomarkers, that indicate if a person has been exposed to smoke to then distinguish between a group of non-smokers and disease-free tobacco smokers. They will test for the presence of these chemicals in smokers' blood, urine, and breath. These studies will provide important base-line data for subsequent studies that will relate cigarette smoke exposure to incidence and genetic susceptibility to tobacco-related disease of the lung and cardiovascular system.
The Penn program has already implemented patient recruitment through the participation of Anil Vachani, MD, Assistant Professor of Medicine. It is anticipated that substantial new information will become available on the presence of various biomarkers so that Andrea Troxel, PhD, Associate Professor of Biostatistics, can assess their potential utility. In addition to determining conventional lipid and DNA biomarkers, a discovery program will be implemented in collaboration with Don Baldwin, PhD, Director of the Penn Microarray Core Facility, in order to identify potential protein biomarkers.
The Principal Investigators from each of the funded projects in the GEI will meet at the National Institutes of Health in December 2007 so that the projects can benefit from the individual expertise of the various participants. Annual meetings between the investigators will then take place over the course of the four years of funded research. It is anticipated that panels of new biomarkers will emerge from these meetings and that the biomarkers will prove to be critical for future studies designed to monitor the adverse effects of gene-environment interactions.
The Penn studies will be complimentary to an earlier award made by the Pennsylvania Department of Health to the CEET, which aims to identify lung cancer susceptibility genes in smokers.
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