Radiotherapy Can Cause Lasting Vascular Disease

For an as yet unknown reason, cancer radiotherapy can increase the risk of cardiovascular disease later in life, a problem that is growing as more and more people survive their cancer diagnosis.

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New research from Karolinska Institutet now suggests that sustained inflammation induced by post-radiotherapy changes in the gene expression in the arteries could be the cause.

Epidemiological 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 biological causes of these serious side effects, which often only appear many years following treatment.

"Studies have been hampered by the fact that the disease process is so slow," says Martin Halle, a researcher at Karolinska Institutet. "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, Martin Halle and colleagues have now managed to study radiotherapy's long-term effects on human blood vessels for the first time. This autograft involves the transplantation of skin, muscle, or bone tissue from one part of a patient's body to reconstruct defects that arise after removing a tumor in another, often irradiated, part.

By harvesting biopsies from previously irradiated branches of the carotid arteries and non-irradiated arteries from grafts, the researchers have been able to compare the difference in global gene expression between irradiated and non-irradiated arteries from the same patient at the same time.

They found that the irradiated arteries showed signs of chronic inflammation and increased activity of Nuclear Factor- kappaB (NF-kappaB), a transcription factor known for playing a key part in the development of atherosclerosis. The greater inflammatory gene expression was visible for several years after irradiation and might, the researchers believe, explain 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 anti-inflammatory treatment," says Dr. Halle.

The importance of the results is underscored by the publication of an explanatory commentary in the journal's editorial.

Publication

"Sustained Inflammation Due to NF-Kappa B Activation in Irradiated Human Arteries," Halle M, Gabrielsen A, Paulsson-Berne G, Gahm C, Agardh HE, Farnebo F, Tornvall P, Journal of the American College of Cardiology, 23 March 2010; 55:1227-1236, doi:10.1016/j.jacc.2009.10.047

Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Karolinska Institutet and published on 2010/03/22, this content may have been edited for style, clarity, or brevity.