Polymorphisms Related to Oxidative Stress Associated With Poorer Cognitive Function After Chemotherapy for Childhood ALL
In a study reported in the Journal of Clinical Oncology, Cole et al found that polymorphisms in genes related to oxidative stress or neuroinflammation were associated with poorer cognitive function in survivors treated for childhood acute lymphoblastic leukemia (ALL). Survivors of childhood ALL have been shown to be at increased risk of neurocognitive deficits.
Study Details
In the study, neurocognitive testing was performed in 350 pediatric ALL survivors treated on Dana-Farber Cancer Institute ALL Consortium protocols. Genomic DNA was obtained from bone marrow collected at remission. Candidate polymorphisms were selected on the basis of the literature, focusing on genes involved in drug metabolism, oxidative damage, altered neurotransmission, neuroinflammation, and folate physiology. Multivariate analysis adjusted for demographic and treatment variables. Patients had a median age of 10 years at neurocognitive testing, at a median of 5 years from diagnosis.
Poorer cognitive or behavioral outcomes were associated with polymorphisms in three genes related to oxidative stress or neuroinflammation: NOS3 (IQ, Q = 0.008; vocabulary, Q = 0.011; matrix reasoning, Q = 0.008), SLCO2A1 (IQ, Q = 0.043; digit span, Q = 0.006; block design, Q = 0.076), and COMT (Behavioral Assessment System for Children-2 attention, Q = 0.080; and hyperactivity, Q = 0.084). Survivors homozygous for NOS3 894T with at least one SLCO2A1 variant G allele or at least one GSTP1 variant allele had lower mean IQ scores vs those without these genotypes.
The investigators concluded: “These data are consistent with the hypothesis that oxidative damage contributes to chemotherapy-associated neurocognitive decline among children with leukemia.”
Peter D. Cole, MD, of Albert Einstein College of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by St Baldrick’s Foundation, National Institutes of Health, and Michael J. Garil Fund for Leukemia Research. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
