Do heart disease and cancer share a genetic link?
Cell growth is controlled, among other things, by various growth factors that bind to receptors in the cell envelope. A mutation in one of these receptors can cause both colon cancer and arteriosclerosis. Heart disease and cancer, two of the leading causes of death in industrialized nations, may share a common genetic cause. That's the view put forward by researchers at Cornell University Medical College. They published their findings in the Journal of Clinical Investigation (November 1 issue). Timothy McCaffrey and his colleagues think that atherosclerosis, like some cancers, could be due to a mutation in a single cell.
We have suspected for decades that cancer and heart disease share the same underlying causes, specifically their tendency to start with the abnormal growth of a single cell, says McCaffrey. We found a specific molecular defect that may be a marker for this process and suggest mechanisms that determine the occurrence of this process."
Arteriosclerosis, or blockage of the coronary arteries, is the most common cause of heart disease. In this disease, soft muscle tissue cells migrate to the inner layer of the blood vessel and proliferate. The uncontrolled growth leads to blockage of the blood vessel. It is also known that the growth factor TGF-beta is a potent inhibitor of cell growth. However, atherosclerosis is resistant to the beneficial effects of TGF-beta.
So McCaffrey and his colleagues decided to look for defects in the gene that encodes one of TGF-beta's cellular receptors: the Type II TGF-beta receptor or RII gene. Their reasoning was based on previous studies by other researchers showing that the RII gene is also altered in tumor cells in the colon, particularly in the gene region that contains a strand of ten adenosine bases (adenosine is one of the four bases that make up the DNA exists). This adenosine-rich region is prone to mutation during DNA replication. These mutations, in turn, cause immunity to the effects of TGF-beta, which can then lead to cancer.
McCaffrey and his colleagues discovered mutations in the same region of the gene in atherosclerotic tissue. This suggests that in some patients the underlying mechanism for both diseases is the same.
McCaffrey's research gives us a new understanding of the two most common diseases associated with aging: cancer and atherosclerosis. The fact that a similar mechanism (i.e., a mutation in a single cell's DNA) can play a role in diseases as diverse as cancer and atherosclerosis suggests that other diseases of aging can also be attributed to a single cell mutation," says drDavid Finkelstein from the National Institute on Aging.
We think these results are important because they open up new avenues for understanding cardiovascular disease, notes McCaffrey. The TGF-beta receptor is a device that normally suppresses excessive cell proliferation, and its deactivation results in slow but uncontrolled growth in the artery.
However, adds McCaffrey, we know of other systems that are also growth suppressing, so it will be very interesting to see if these other systems are affected in patients. By identifying the most commonly compromised systems, we can develop diagnostic and therapeutic strategies that target those systems or optimize treatments that bypass the faulty systems.
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