Scientists from a leading European medical university suggest that the sustained inflammation in the arteries brought on by changes in gene expression as a result of cancer radiotherapy could be the reason why so many people who survive their cancer diagnosis go on to develop cardiovascular disease later in life.

You can read about the study by the team from Sweden’s Karolinska Institutet online in the 23 March issue of the Journal of the American College of Cardiology.

Previous studies have found that cancer radiotherapy increases the risk of cardiovascular disease in the same part of the body. For instance, having radiotherapy to treat breast cancer in the left breast increases the risk of heart attack, and having radiotherapy to treat head and neck tumors increases the risk of a stroke.

However, we know very little about the underlying biology of these serious radiotherapy side-effects, which in most cases don’t develop until many years later.

Dr Martin Halle, a researcher in the Department of Medicine, Center for Molecular Medicine at the Karolinska Institutet in Stockholm, told the press that it has been difficult to do research in this area because the disease takes so long to develop:

“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,” he explained.

However, the researchers found a way to examine the long-term effects of radiotherapy on human blood vessels by studying autografts: where skin, muscle or bone has been transplanted from one part of the body to another in order to reconstruct defects left after a tumor is removed.

Radiotherapy often follows tumor removal (before the graft takes place), so offers the opportunity to recover tissue at the irradiated site from arteries that are in situ before radiotherapy and also from tissue transplanted there afterwards.

Thus Halle and colleagues were able to compare the differences in global gene expression in biopsies taken from the previously irradiated branches of the carotid arteries with biopsies of non-irradiated arteries from grafts from the same patient at the same time.

They found that the arteries that had been exposed to radiotherapy showed signs of chronic inflammation and increased activity of a transcription factor (a protein important for gene expression) that is central to the development of atherosclerosis. The transcription factor is called Nuclear Factor-kappaB (NF-kappaB).

The increased activity in inflammatory gene expression was present several years after the radiotherapy treatment, leading the researchers to suspect that this is why the cardiovascular disease only develops a long time after treatment.

Halle said they hoped these findings will help develop ways to reduce the long term risk of radiotherapy: perhaps by combining it with anti-inflammatory treatment.

“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.

Source: Karolinska Institutet.

Written by: Catharine Paddock, PhD