Gene Linked to Heart Failure

While nearly 80 percent of children treated for cancer survive, these survivors tend to face a variety of health problems as they grow older. Research presented at the American Society of Clinical Oncology meeting in June showed that one of these problems—cardiomyopathy, a condition where the heart cannot pump properly—was tied to a specific gene and drug dose.

The research shows that survivors who carry particular inherited variants of the carbonyl reductases (CBR) gene and received low doses of anthracycline chemotherapy were more likely to develop heart problems than those without the CBR gene.

Currently, anthracyclines form the backbone of childhood cancer therapy, as anthracyclines are incorporated into the chemotherapy regimen of more than 50 percent of childhood cancer patients. Researchers already knew that there was a dose-dependent relationship between anthracyclines and congestive heart failure and that the two-year survival after developing congestive heart failure was less than 50 percent.

“But what we also noticed is that certain children who receive very low doses develop heart failure,” says Smita Bhatia, MD, MPH, of City of Hope National Medical Center and study lead. “We were therefore interested in knowing what increased the risk of anthracycline-related cardiomyopathy.”

In a case-control study, Bhatia and her colleagues found that in patients who received low drug doses, those with the CBR1 variant were about five times more likely to develop heart problems, while those with the CBR3 variant were about three times at higher risk.

Researchers believe that this discovery could lead to a more personalized approach to preventing toxicities associated with anthracyclines—doctors can screen patients for the CBR gene, and then prescribe non-cardiotoxic alternatives.