DUARTE, Calif., November 28, 2011 — City of Hope researchers have found that a specific group of pediatric cancer survivors have a higher chance of developing congestive heart failure after undergoing a treatment with anthracycline chemotherapy. The study, published in the Journal of Clinical Oncology, found that a specific variation of the CBR3 gene is linked to the development of cardiovascular complications. Investigators are conducting further research to develop tests and treatment guidelines that may reduce or mitigate this risk.
“We observed that some children tolerated high doses of anthracyclines, a class of drugs used to treat leukemia, lymphoma and other cancers, while others experienced heart problems even after low doses,” said Smita Bhatia, M.D., M.P.H., Ruth Ziegler Chair in Population Sciences at City of Hope and senior author of the paper, “so our team investigated to see if there is a genetic factor that explains this difference.”
In the study, Bhatia and her colleagues observed 487 childhood cancer survivors who had received anthracycline therapy and compared those who had developed cardiomyopathy, or life-threatening weakening of the heart muscle, and those who did not. Previous research in laboratory and animal studies had shown that variations of two genes, CBR1 and CBR3, are linked to drug-related cardiomyopathy by influencing the production of an enzyme that breaks down anthracyclines into an alcohol compound that damages heart tissue.
After analysis, they found that survivors carrying a “GG” variant in a specific portion of the CBR3 gene faced a high likelihood of developing cardiomyopathy especially among those exposed to moderate doses of anthracycline drugs. This risk is significantly greater than those carrying the other two variants in that portion of the gene, “AA” and “AG”.
“About 50 percent of African-Americans and 30 percent of Caucasians carry the GG variant, so this isn’t a negligible group.” Bhatia said, noting that data on other ethnic groups are not available yet.
Bhatia also added that because 50 percent of frontline cancer regimens include anthracyclines, drug-related cardiomyopathy is a significant problem among cancer survivors. With these findings, Bhatia and her team hope to develop tests that can determine a patient’s CBR3 status, allowing physicians to adjust treatment, monitoring and follow-up care to protect the patient’s heart.
The researchers are also planning further studies to identify other genes that may play a role in drug-related cardiomyopathy.
The study’s lead authors were Can-Lan Sun, M.D., Ph.D., associate research scientist in City of Hope’s Department of Population Sciences and Javier G. Blanco, Ph.D., assistant professor of pharmaceutical sciences at State University of New York, Buffalo. Funding for this research came from the National Cancer Institute, Lance Armstrong Foundation, National Institute of General Medical Sciences (NIGMS), The Leukemia & Lymphoma Society, National Institutes of Health/NIGMS Pharmacogenomics Research Network and American Lebanese Syrian Associated Charities.
