Evidence map›Paper›PMID 25987702›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015

Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia.

Peter D Cole, Yaron Finkelstein, Kristen E Stevenson, Traci M Blonquist, Veena Vijayanathan, Lewis B Silverman, Donna S Neuberg, Stephen E Sallan, Philippe Robaey, Deborah P Waber

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Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Pooled it
  4. Trial
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  7. Feasibility of baseline neurocognitive assessment using Cogstate during the first month of therapy for childhood leukemia.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2017
    Trial
  8. Review
  9. Article
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  12. Cognitive dysfunction in chemobrain: Molecular mechanisms and therapeutic implications.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
    Review
  13. Review
  14. Article
  15. Systemic Biological Mechanisms of Neurocognitive Dysfunction in Long-Term Survivors of Childhood Hodgkin Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  16. Article
  17. Article
  18. Chemobrain: An accelerated aging process linking adenosine AInternational review of neurobiology · 2023
    Review
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  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Peter D ColePeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA. Peter.Cole@Einstein.YU.edu.
Yaron FinkelsteinPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Kristen E StevensonPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Traci M BlonquistPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Veena VijayanathanPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Lewis B SilvermanPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Donna S NeubergPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Stephen E SallanPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Philippe RobaeyPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.
Deborah P WaberPeter D. Cole, Veena Vijayanathan, Albert Einstein College of Medicine, Bronx, NY; Yaron Finkelstein, Hospital for Sick Children, University of Toronto, Toronto; Philippe Robaey, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Kristen E. Stevenson, Traci M. Blonquist, Donna S. Neuberg, Dana-Farber Cancer Institute (DFCI); Lewis B. Silverman, Stephen E. Sallan, DFCI, Boston Children's Hospital, Harvard Medical School; and Deborah P. Waber, DFCI, Harvard Medical School, Boston, MA.

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
Zebrafish Screens for Genetic Modifiers and Human Application in T-ALLP01CA068484 · NCI · DANA-FARBER CANCER INSTITUTE · PI ARMSTRONG, SCOTT A · 1995 to 2010
$31.9M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
NCI NIH HHS P01 CA068484NCI NIH HHS P30 CA013330NICHD NIH HHS IH P30 HD18655NICHD NIH HHS P30 HD018655
6 · The paper itself

Abstract

purposeSurvivors of childhood acute lymphoblastic leukemia (ALL) exhibit increased rates of neurocognitive deficits. This study was conducted to test whether interpatient variability in neurocognitive outcomes can be explained by polymorphisms in candidate genes conferring susceptibility to neurocognitive decline.

methodsNeurocognitive testing was conducted in 350 pediatric leukemia survivors, treated on Dana-Farber Cancer Institute ALL Consortium Protocols 95-01 or 00-01. Genomic DNA was isolated from bone marrow collected at remission. Candidate polymorphisms were selected on the basis of prior literature, targeting genes related to drug metabolism, oxidative damage, altered neurotransmission, neuroinflammation, and folate physiology. Single nucleotide polymorphisms were detected using either a customized multiplexed Sequenom MassARRAY assay or polymerase chain reaction-based allelic discrimination assays. Multivariable logistic regression models were used to estimate the effects of genotype on neurocognitive outcomes, adjusted for the effects of demographic and treatment variables. False-discovery rate correction was made for multiple hypothesis testing, indicated as a Q value.

resultsInferior cognitive or behavioral outcomes were associated with polymorphisms in three genes related to oxidative stress and/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 with at least one GSTP1 variant allele, had lower mean estimated IQ scores than those without these genotypes.

conclusionThese data are consistent with the hypothesis that oxidative damage contributes to chemotherapy-associated neurocognitive decline among children with leukemia.

Indexed as

Polymorphism, Single NucleotideAdolescentAllelesChildChild, PreschoolCognition DisordersFemaleGenotypeHumansInfantMaleNeuropsychological TestsOxidative StressPolymerase Chain ReactionPrecursor Cell Lymphoblastic Leukemia-LymphomaSurvivors

Identifiers

PMID25987702
PMCPMC4477790

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.