Do Heart Disease and Cancer Have a Common Genetic Link?
Researchers at Cornell University Medical College Identify Genetic Marker
Nov 12, 1997
Heart disease and cancer, the two leading causes of death in the US, may have a common genetic cause, according to researchers at Cornell University Medical College. Their findings are published in the November 1 issue of the Journal of Clinical Investigation.
Lead author Dr. Timothy McCaffrey and his colleagues suggest that atherosclerosis, like some forms of cancer, may be linked to a mutation in a single cell that could spread and cause disease. Atherosclerosis, or blockage of the coronary arteries, is the most common cause of heart disease.
"We have suspected for decades that cancer and heart disease have similar underlying causes, particularly their tendency to derive from the abnormal growth of a single cell," said Dr. McCaffrey. "Our finding is a precise molecular defect that may be one marker for this process and may also suggest mechanisms by which this process may occur."
In atherosclerosis, smooth muscle tissue cells migrate to the inner layer of the blood vessel, and proliferate and multiply. This uncontrolled growth causes blockage of the blood vessel. It is also known that the growth factor protein TGF-beta is a potent inhibitor of cell growth; however, atherosclerotic tissue is resistant to TGF-beta's beneficial effects.
Therefore, McCaffrey and his colleagues decided to look for defects in the gene that encodes one of the cellular receptors of TGF-beta, the Type II TGF-beta receptor or RII gene. Their reasoning was based on previous studies by other investigators that showed that the RII gene is also altered in colon cancer tumors, specifically in the area of the gene containing a stretch of ten adenosine bases (adenosine is one of the four bases that make up DNA). This adenosine-rich region is prone to errors, also called mutations, during the replication of the DNA. And these mutations cause resistance to the effects of TGF-beta which can lead to cancer. Dr. McCaffrey and his colleagues discovered mutations in the same area of the gene in atherosclerotic tissue, which suggests that the same mechanism underlies both diseases, in some patients. Dr. McCaffrey's research gives us a new understanding of two of the most common diseases associated with aging—cancer and atherosclerosis.
"The fact that a similar mechanism (i.e., a mutation in the DNA of a single cell) could play a part in diseases as diverse as cancer and atherosclerosis suggests that other diseases of aging might also be traced back to a similar single-cell mutation," said Dr. David Finkelstein, PhD, of the National Institute on Aging.
"We believe that these results are important because it gives us new avenues toward understanding the progression of cardiovascular disease," said Dr. McCaffrey. "The TGF-beta receptor is one pathway that normally suppresses cell proliferation, and its inactivation leads to slow, but uncontrolled, growth in the artery."
"However," he added, "We know that there are other systems that also can suppress growth, and so it will be very interesting to see if those systems are affected in patients. By determining the most common pathways that are affected, we can design diagnostic and therapeutic strategies that target those systems, or optimize treatments that circumvent these defective pathways."
This study reflects the close collaboration of basic scientists with cardiologists and vascular surgeons, including Dr. Timothy Sanborn and Dr. Harry Bush, both of The New York Hospital-Cornell Medical Center. Dr. McCaffrey's research was supported by the National Heart, Lung, and Blood Institute and the National Institute on Aging.
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