Evidence map›Paper›PMID 26799497›Full record

Observational studyPharmacogenomics2016

Evidence for association of SNPs in ABCB1 and CBR3, but not RAC2, NCF4, SLC28A3 or TOP2B, with chronic cardiotoxicity in a cohort of breast cancer patients treated with anthracyclines.

Daniel L Hertz, Megan V Caram, Kelley M Kidwell, Jacklyn N Thibert, Christina Gersch, Nicholas J Seewald, Jeffrey Smerage, Melvyn Rubenfire, N Lynn Henry, Kathleen A Cooney and 3 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Pharmacogenomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 3 pooled it
4.3field-weighted citation impact, top 5% 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

50 citing papers in PubMed, 3 syntheses or guidelines pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Review
  6. Review
  7. Gain-of-Function VariantCirculation. Genomic and precision medicine · 2026
    Article
  8. Review
  9. Observational
  10. Article
  11. Review
  12. Review
  13. Article
  14. Genetic factors in the pathogenesis of cardio-oncology.Journal of translational medicine · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
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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

13 authors at 2 institutions in 1 country.

Daniel L HertzDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.
Megan V CaramDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kelley M KidwellDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Jacklyn N ThibertDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Christina GerschDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Nicholas J SeewaldDepartment of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Jeffrey SmerageDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Melvyn RubenfireDepartment of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
N Lynn HenryDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Kathleen A CooneyDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Monika LejaDepartment of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jennifer J GriggsDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
James M RaeDepartment of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
University of Michigan–Ann Arbor · USMichigan Medicine · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Genetic Predictors of Anti-Estrogen Clinical Activity in Breast Cancer PatientsR01GM099143 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAE, JAMES MICHAEL · 2011 to 2015
$1.6M
NCATS NIH HHS UL1 TR000433NCI NIH HHS P30 CA046592NIGMS NIH HHS 1R01GM099143NIGMS NIH HHS R01 GM099143
6 · The paper itself

Abstract

aimsValidation of associations for SNPs in RAC2, NCF4 and SLC28A3, identification of a novel association with a TOP2B SNP and screening 23 SNPs putatively relevant to anthracycline-induced cardiotoxicity. PATIENTS &

methodsA total of 166 breast cancer patients treated with doxorubicin underwent echocardiogram, including 19 cases with systolic dysfunction (ejection fraction <55%) and 147 controls. Four high priority SNPs were tested in the primary analysis, with appropriate statistical correction, and 23 additional SNPs were screened in an uncorrected secondary analysis.

resultsPreviously reported associations for RAC2, NCF4 and SLC28A3 could not be validated and a novel association with TOP2B was not discovered in this cohort (all p > 0.05), likely due to inadequate power. Two SNPs were identified in the uncorrected secondary analysis including a protective SNP in ABCB1 (3435C>T, p = 0.049) and a risk allele in CBR3 (V244M, p = 0.012).

conclusionThe associations reported in prior publications and those discovered in this secondary analysis require further replication in independent cohorts.

Indexed as

Alcohol OxidoreductasesAnthracyclinesAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BBreast NeoplasmsCardiotoxicityCase-Control StudiesChronic DiseaseCross-Sectional StudiesDNA-Binding ProteinsDNA Topoisomerases, Type IIFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHumansMembrane Transport ProteinsABCB1 protein, humanAlcohol OxidoreductasesAnthracyclinesAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BCBR3 protein, humancif nucleoside transporterDNA-Binding ProteinsDNA Topoisomerases, Type IIMembrane Transport ProteinsNADPH OxidasesNCF4 protein, humanPoly-ADP-Ribose Binding ProteinsRAC2 GTP-Binding Proteinrac GTP-Binding ProteinsTOP2B protein, humanABCB1anthracyclinecardiotoxicityCBR3doxorubicinNCF4pharmacogeneticRAC2SLC28A3systolic dysfunctionTOP2B

Identifiers

PMID26799497
PMCPMC5558515
OpenAlexW2280906963

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.