Genes variations raise risk of heart disease after treatment for childhood cancer

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.