Anthracycline-related cardiomyopathy risk is elevated by a genetic variation

 By Hannah Echols

Jan 09 2023

Cardiomyopathy is more likely to occur in childhood cancer survivors who have two genetic variants in the ROBO2 gene and who received high doses of anthracycline therapy.

Anthracyclines, a chemotherapy drug used to treat a variety of paediatric cancer forms, have been shown to cause exposure in around 60% of children cancer survivors. Studies have demonstrated a substantial dose-dependent relationship between anthracycline exposure and cardiomyopathy, a condition that affects the heart's ability to pump blood to the body's other organs. Heart failure can be caused by cardiomyopathy.

Researchers from the University of Alabama in Birmingham found a relationship between the genetic mutation ROBO2 and an elevated risk of developing anthracycline-related cardiomyopathy in findings published in the Journal of Clinical Oncology.

Smita Bhatia, M.D., director of the UAB Institute for Cancer Outcomes and Survivorship and senior author, stated that "we found two genetic polymorphisms in the ROBO2 gene that exhibited a strong gene-anthracycline interaction impact." These changes increased the likelihood of cardiomyopathy or heart failure in individuals by a factor of two to eight.

The ROBO2 gene is a robo receptor that binds ligands associated with cell adhesion, proliferation, and survival known as Slit guidance ligands. Slit-Robo signalling is engaged in a number of heart development-related processes. It was shown that the Slit-Robo stimulated cardiac fibrosis via the TGF-b1/Smad signalling pathway, which can result in cardiac dysfunction and heart failure.

According to Bhatia's research, individuals with anthracycline exposure and ROBO2 polymorphisms may have a reduction in the risk of cardiomyopathy and a suppression of cardiac fibrosis if Robo signalling and/or TGF-b1/Smad signalling are suppressed.