Evidence map›Paper›PMID 26345518›Full record

Trial reportThe pharmacogenomics journal2016

Polymorphisms of ABCC5 and NOS3 genes influence doxorubicin cardiotoxicity in survivors of childhood acute lymphoblastic leukemia.

M Krajinovic, J Elbared, S Drouin, L Bertout, A Rezgui, M Ansari, M-J Raboisson, S E Lipshultz, L B Silverman, S E Sallan and 5 more

Abstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The pharmacogenomics journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 3 pooled it
6.4field-weighted citation impact, top 3% of its field
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

53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Cardioprotective Potential ofCurrent drug targets · 2026
    Article
  6. Article
  7. Review
  8. Genetic factors in the pathogenesis of cardio-oncology.Journal of translational medicine · 2024
    Review
  9. Review
  10. Article
  11. Article
  12. Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024
    Review
  13. Article
  14. Review
  15. Cardio-oncology for Pediatric and Adolescent/Young Adult Patients.Current treatment options in oncology · 2023
    Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. Review
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

15 authors at 5 institutions in 2 countries.

M KrajinovicCHU Sainte-Justine Research Center, Montreal, QC, Canada.
J ElbaredCHU Sainte-Justine Research Center, Montreal, QC, Canada.
S DrouinCHU Sainte-Justine Research Center, Montreal, QC, Canada.
L BertoutCHU Sainte-Justine Research Center, Montreal, QC, Canada.
A RezguiCHU Sainte-Justine Research Center, Montreal, QC, Canada.
M AnsariCHU Sainte-Justine Research Center, Montreal, QC, Canada.
M-J RaboissonCHU Sainte-Justine Research Center, Montreal, QC, Canada.
S E LipshultzDepartment of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, USA.
L B SilvermanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, MA, USA.
S E SallanDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
D S NeubergMolecular Pathology, Infinity Pharmaceuticals, Cambridge, MA, USA.
J L KutokDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
C LaverdièreCHU Sainte-Justine Research Center, Montreal, QC, Canada.
D SinnettCHU Sainte-Justine Research Center, Montreal, QC, Canada.
G AndelfingerCHU Sainte-Justine Research Center, Montreal, QC, Canada.
Centre Hospitalier Universitaire Sainte-Justine · CADana-Farber Cancer Institute · USUniversité de Montréal · CAInfinity Pharmaceuticals (United States) · USWayne State University · US

Funding

CIHR
6 · The paper itself

Abstract

Anthracyclines are efficient chemotherapy agents. However, their use is limited by anthracycline-induced cardiotoxicity (CT). We investigated the influence of polymorphisms in doxorubicin metabolic and functional pathways on late-onset CT as estimated by echocardiography in 251 childhood acute lymphoblastic leukemia (cALL) patients. Association analyses revealed a modulating effect of two variants: A-1629 T in ABCC5, an ATP-binding cassette transporter, and G894T in the NOS3 endothelial nitric oxide synthase gene. Individuals with the ABCC5 TT-1629 genotype had an average of 8-12% reduction of ejection (EF) and shortening fractions (SF; EF: P<0.0001, and SF: P=0.001, respectively). A protective effect of the NOS3 TT894 genotype on EF was seen in high-risk patients (P=0.02), especially in those who did not receive dexrazoxane (P=0.002). Analysis of an additional cohort of 44 cALL patients replicated the ABCC5 association but was underpowered for NOS3. In summary, we identified two biomarkers that may contribute to cALL anthracycline CT risk stratification.

Indexed as

Pharmacogenomic VariantsPolymorphism, Single NucleotideAdolescentAdultAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsCardiotonic AgentsCardiotoxicityChildChild, PreschoolDexrazoxaneDoxorubicinFemaleGenetic Predisposition to DiseaseHeart DiseasesHeterozygoteABCC5 protein, humanAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsCardiotonic AgentsDexrazoxaneDoxorubicinNitric Oxide Synthase Type IIINOS3 protein, human

Identifiers

PMID26345518
OpenAlexW1796210937

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.