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Genes raise risk of heart disease after treatment for childhood cancer
June 05, 2006Research 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.
Children's Hospital of Philadelphia
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.
Children's Hospital of Philadelphia
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Childhood cancer survivors less likely to marry, Yale researchers find
Adult survivors of childhood cancer are 20 to 25 percent more likely to never marry compared with siblings and the general population, Yale School of Medicine researchers report in a new study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
Brain tumors in childhood leave a lasting mark on cognition, life status
Brain tumors in childhood cast a long shadow on survivors. The first study of the lasting impact of these tumors -- the most common solid malignancies in childhood -- shows that survivors have ongoing cognitive problems.
Childhood cancer survivors experience suicidal thoughts decades after diagnosis
Adult survivors of childhood cancer have an increased risk for suicidal thoughts, even decades after their cancer treatments ended, according to a study led by Dana-Farber Cancer Institute scientists.
Survivors of childhood cancer less likely to marry
Childhood cancer survivors typically suffer from the long-term effects of cancer treatment on physical health, and results of a new study suggest that social implications also exist, which may affect their chance of an "I do" at the altar.
New treatment more than doubles survival for high risk childhood leukemia
Results of a phase two clinical trial published October 5th in the Journal of Clinical Oncology show that adding continuous daily doses of a targeted drug called imatinib mesylate to regular chemotherapy more than doubled three-year survival rates for children with a high risk type of blood cancer called Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
Studies find few risks to newborn offspring of parents who are childhood cancer survivors
Whether they can have children is one of the major concerns for adult survivors of childhood and adolescent cancer because fertility can be compromised by cancer treatment.
Scientists link genetic glitches to common childhood cancer
A multicenter team of childhood cancer researchers has discovered two genetic variations linked to an increased risk for acute lymphoblastic leukemia, or ALL, the most common childhood cancer in the United States.
Inherited risk factors increase odds of developing childhood acute lymphoblastic leukemia
Scientists at St. Jude Children's Research Hospital have identified inherited variations in two genes that account for 37 percent of childhood acute lymphoblastic leukemia (ALL), including a gene that may help predict drug response.
Cancer Mortality Rates Experience Steady Decline
The number of cancer deaths has declined steadily in the last three decades. Although younger people have experienced the steepest declines, all age groups have shown some improvement, according to a recent report in Cancer Research, a journal of the American Association for Cancer Research.
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