Cancer Agents & Kids: How Genes Influence Adverse Effects

Certain genes appear to influence cancer treatment’s impact on I.Q., behavior and other neurological parameters in children, according to a study led by Peter D. Cole, M.D., associate professor of pediatrics (hematology & oncology) at Albert Einstein College of Medicine and chief of the hematologic malignancy service at the Children’s Hospital at Montefiore.

Treatment for acute lymphoblastic leukemia (ALL) almost always cures the disease but can leave children with cognitive deficits that later lead to academic and behavioral problems. Previous research has hinted that genetic differences may explain why some children suffer these adverse effects while others don’t.

Dr. Cole, a pediatric oncologist, looked for genes that may be implicated in treatment-induced cognitive decline. In a study involving 350 children treated for ALL, he and his colleagues discovered connections between cognitive/behavioral problems and genes related to the oxidative stress caused by chemotherapy.

Among the most specific links discovered were those between endothelial nitric oxide synthase (the NOS3 gene) and IQ, vocabulary and reasoning; catechol-O-methyltransferase (COMT) and attention and hyperactivity; and prostaglandin transporter (SLCO2A1) and IQ.

“Our findings support the hypothesis that neurocognitive decline in children with ALL may be related to oxidative damage from chemotherapy,” says Dr. Cole. “Children with genetic variations that permit this oxidative damage may be candidates for antioxidant therapy.”

The study was published online May 18 in the Journal of Clinical Oncology. The other authors are Veena Vijayanathan, Ph.D., an associate in pediatrics (hematology and oncology) at Einstein, and researchers from the Hospital for Sick Children in Toronto; the Children’s Hospital of Eastern Ontario in Ottawa; and the Dana-Farber Cancer Institute and Harvard Medical School in Boston.

National Institutes of Health grant funding supports Dr. Cole’s work.