Genes raise risk of heart disease after treatment for childhood cancer

Research builds groundwork for finding personalized, less toxic cancer drugs

Gene variations may raise the risk that survivors of childhood cancer will suffer congestive heart failure as a complication of drugs they received during cancer treatment.

Richard Aplenc, M.D., a pediatric oncologist at The Children's Hospital of Philadelphia, reported on a study of childhood cancer survivors in a presentation today at the American Society of Clinical Oncology (ASCO) annual meeting in Atlanta. He led the research, drawing on data from the Childhood Cancer Survivor Study, a long-term national study sponsored by the National Cancer Institute.

The researchers studied anthracyclines, a commonly used class of anticancer drugs known to cause heart damage in some patients. The research team investigated two groups of childhood cancer survivors, all of whom had been treated with anthracyclines. The study compared 47 patients with congestive heart failure (CHF) to a control group of 195 patients without CHF.

The researchers investigated 10 polymorphisms, naturally occurring variants in DNA bases called nucleotides, in seven genes they identified as having a role in biological responses to anthracyclines. "We found that polymorphisms in the GSTP gene significantly increased a patient's risk for CHF after treatment with anthracyclines," said Dr. Aplenc. One polymorphism increased risk by five times; another variant was linked to a tripling of risk.

The research group chose particular genes as candidates for study because those genes carry the codes for enzymes involved in metabolizing anthracyclines and the reactive oxygen molecules that anthracyclines produce. If physicians can better classify gene variations that modify side effects of anticancer drugs, they may be able to better tailor treatment plans to individual patients. Thus, knowledge of a patient's genetic makeup may allow physicians to select a more personalized, less toxic treatment.

"Further study needs to be done, using larger numbers of patients, to determine if these results hold up," said Dr. Aplenc. "We hope these findings will provide a scientific foundation for safer, more effective cancer treatments for children."

Dr. Aplenc's research abstract was featured in a news conference at the ASCO meeting, which this year has a special focus on cancer survivors. Dr. Aplenc is an attending oncologist at Children's Hospital, where he researches gene variations in the enzymes that interact with chemotherapy drugs in children.

Co-authors of the study were Javier Blanco, Wendy Leisenring, Stella Davies, Mary Relling, Leslie Robison, Charles Sklar, Marilyn Stovall and Smita Bhatia.

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About the Oncology Program at The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia cares for more children with cancer than any other general pediatric hospital in the United States. Its extensive basic and clinical research programs have been recognized recently by Child Magazine, which ranked Children's Hospital first in the nation in pediatric oncology. Researchers at Children's Hospital have had pioneering roles in studying survivors of childhood cancer, and have changed medical practice to reduce late adverse effects of cancer treatment. Clinicians here also lead programs that help the expanding pool of cancer survivors and their families meet the special medical and psychological challenges of survivorship. For more information about the Cancer Survivorship Program at Children's Hospital, visit www.chop.edu/survivorship.

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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