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Children with particular variants of drug-metabolizing genes may be more likely than other children to develop heart problems after low doses of anthracycline chemotherapy. The results of this study will be presented at the 2010 annual meeting of the American Society of Clinical Oncology.

Anthracyclines are commonly used chemotherapy drugs that can have adverse effects on the heart. A potential late effect of anthracycline treatment is cardiomyopathy, in which the heart does not pump efficiently.

Enzymes known as carbonyl reductases (CBR) play a role in metabolizing anthracyclines into substances that can damage the heart. Variability in CBR-producing genes may explain why some people develop anthracycline-related heart problems and others don’t.

To explore the relationship between variants in two CBR genes—CBR1 and CBR3—and risk of anthracycline-related heart problems, researchers conducted a study among 165 childhood cancer survivors with cardiomyopathy and 323 childhood cancer survivors with no heart disease. Study participants had been diagnosed with cancer between 1966 and 2008.

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  • Among those treated with high doses of anthracyclines (greater than 250 mg/m2), CBR gene variants had little effect on risk of heart problems. The researchers speculate that at high doses of anthracyclines, heart toxicity is driven by other mechanisms.
  • Among those treated with low doses of anthracyclines, CBR gene variants significantly increased risk of heart problems. The CBR1 gene variant increased the risk of heart problems by more than five-fold, and the CBR3 gene variant increased risk by more than three-fold.

The researchers hope that this study will eventually contribute to more personalized treatment of childhood cancer. If confirmed, these findings suggest that children at high risk of anthracycline-related heart problems may benefit from alternative approaches to treatment or follow-up.

Reference: Blanco JG, Sun C, Landier W et al. Anthracycline-related cardiomyopathy in childhood cancer survivors and association with polymorphisms in the carbonyl reductase genes: A Children’s Oncology Group study. To be presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 9512.

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