Radiotherapy Shown to Cause Lasting Vascular Disease

For a yet unknown reason, cancer radiotherapy can increase the risk of cardiovascular disease later in life, a predicament that is growing as more people survive their cancer diagnosis. New research out of Sweden now suggests that sustained inflammation induced by postradiotherapy alters the gene expression in the arteries.

Epidemiologic studies have shown that a course of radiotherapy increases the risk of cardiovascular disease in the same part of the body; for example, myocardial infarction after left side breast cancer treatment, or stroke after the treatment of head and neck or brain tumors. Scientists know very little, however, about the biologic causes of these serious side effects, which frequently do not present until many years following treatment.

"Studies have been hampered by the fact that the disease process is so slow,” stated Dr. Martin Halle, a researcher from the Karolinska Institutet (Stockholm, Sweden). "Cell studies and animal studies are best suited to the more immediate effects, and studies on human subjects have been ruled out for ethical reasons.”

By studying autografts that have been carried out after cancer, Dr. Halle and colleagues have now for the first time managed to evaluate the long-term effects of radiotherapy on human blood vessels. This type of autograft involves the transplantation of skin, muscle, or bone tissue from one part of a patient's body to reconstruct defects that arise after the removal of a tumor in another, often irradiated, area. By harvesting biopsies from previously irradiated branches of the carotid arteries and nonirradiated arteries from grafts, the researchers have been able to compare the difference in global gene expression between irradiated and nonirradiated arteries from the same patient at the same time.

The investigators discovered that the irradiated arteries showed signs of chronic inflammation and an increase in activity of nuclear factor-kappaB (NF-kappaB), a transcription factor known for playing a major part in the development of atherosclerosis. The greater inflammatory gene expression was visible for several years after irradiation, and might, the researchers believe, clarify why cancer patients can suffer cardiovascular disease many years after radiotherapy.

"Hopefully, these findings will one day help medicine to mitigate the side effects by administering radiotherapy in combination with an anti-inflammatory treatment,” said Dr Halle.

The study's findings were published in the March 23, 2010, issue of the Journal of the American College of Cardiology. The importance of the results is underscored by the publication of an explanatory commentary in the journal's editorial.

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