Heart disease in childhood cancer survivors linked to gene variations

Childhood cancer survivors who received low doses of anthracycline chemotherapy and who also had variations in a gene called CBR were more likely to develop heart disease than survivors without CBR gene variations who received low doses, according to research presented today at the American Society of Clinical Oncology's annual meeting.CBRs, or carbonyl reductases, help metabolize anthracycline drugs into substances that can damage the heart. The activity of CBRs can be affected by variations in the CBR-producing genes CBR1 and CBR3, both of which were used in the study to determine the risk of heart disease.Researchers compared 165 survivors who developed cardiomyopathy, in which the heart doesn't pump effectively, with 323 survivors without heart disease. Most of the patients included in the study were treated after 1981, with a median age of 7.5 years at diagnosis.For survivors treated with high doses of anthracyclines, the CBR gene variations didn't have much effect on the risk of heart disease because the high dose meant the risk was already high. But for those who received a low anthracycline dose, carrying the CBR1 gene variation resulted in a 5.3-fold increased risk for cardiomyopathy compared to those with the low-risk gene variation. Survivors with the CBR3 gene variation had a 3.1-fold increased risk. "Although we depend heavily on anthracyclines for treating children with cancer, we are fully aware of their toxic effects to the heart. We also know that some patients--despite being exposed to higher doses--don't develop heart problems, while others with little exposure have considerable cardiac damage," senior author Smita Bhatia, MD, of the City of Hope National Medical Center in Duarte, California, said in a press statement.More research is needed, Bhatia said in a press briefing prior to the meeting, but if the findings hold, she said pediatric oncologists can use a personalized approach based on knowledge of the patient's genetic makeup. She said children with cancer could be screened for these gene variations before treatment, and therapy that doesn't include anthracyclines could be considered for patients at risk for heart disease.The mechanisms behind the CBR gene variations and increased risk for heart disease are the same in adults as in childhood cancer patients, said Bhatia, adding that her institution is currently doing similar research in adults.Because childhood cancer survivors can experience various late effects of cancer treatment, the Children's Oncology Group developed follow-up guidelines that provide recommendations for screening and management of possible late effects. The guidelines can be downloaded at www.survivorshipguidelines.org. Melissa Weber is the former managing editor of CURE and is covering the annual meeting of the American Society of Clinical Oncology.