The
Cardiomyopathy
Association

Children who receive low dose chemotherapy have up to five times the risk of developing cardiomyopathy if they have mutations on particular genes, a study has found.  But if they have high doses of chemotherapy, the risk is similar whether they have the variants or not.

It has long been known that some children who have chemotherapy as part of their cancer treatment will develop cardiomyopathy in later life while others don’t. The study at the City of Hope Medical Centre in California looked at why this might be.

Dr Smita Bhatia and her team hypothesized that there was some inherent genetic susceptibility that raised the risk.

They found that in low dose anthracycline chemotherapy those with variants on the carbonyl reductase (CBR) gene were at greater risk.

The study, in which 121 centres took part, included 165 childhood cancer survivors with documented cardiomyopathy and 323 with no cardiomyopathy. The study was conducted as part of the Children's Oncology Group's work.

The children were diagnosed between 1966 and 2008, with approximately 80 per cent treated after 1981.

Of the children, 162 had acute leukemia, 111 lymphoma, 120 sarcoma and 93 had other cancers. The median age at diagnosis was 7.5 years and the median time to a diagnosis of cardiomyopathy was 7.1 years.

The researchers found that among those with cardiomyopathy who had been treated with high doses (greater than 250 mg/m2) of anthracyclines, the CBR genes had little effect on heart disease risk, which was already high because of the large dose of drug.

However, the CBR genes affected cardiomyopathy risk at lower doses (less than 250 mg/m2) of anthracyclines.

Children who had variants in the CBR1 gene had a 5.3-fold increased risk, and those who had variants in the CBR3 gene had a 3.1-fold increased risk.

"This is the largest cohort of documented childhood cancer-related cardiomyopathy," noted Dr. Bhatia. “With lower doses of anthracyclines, CBR genes play a critical role in modulating the risk of cardiotoxicity."