Evidence map›Paper›PMID 18451141›Full record

ArticleCancer research2008

Genetic variants contributing to daunorubicin-induced cytotoxicity.

R Stephanie Huang, Shiwei Duan, Emily O Kistner, Wasim K Bleibel, Shannon M Delaney, Donna L Fackenthal, Soma Das, M Eileen Dolan

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Analysis ofInternational journal of molecular sciences · 2024
    Article
  5. Article
  6. Article
  7. Article
  8. Association of Genetic Variants atFrontiers in cardiovascular medicine · 2020
    Article
  9. Review
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  11. Review
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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

8 authors at 2 institutions in 2 countries.

R Stephanie HuangDepartment of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Shiwei Duan
Emily O Kistner
Wasim K Bleibel
Shannon M Delaney
Donna L Fackenthal
Soma Das
M Eileen Dolan
Immunovaccine (Canada) · CAUniversity of Chicago · US

Funding

Whole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI RATAIN, MARK J · 2000 to 2014
$39.0M
THE STANFORD PHARMACOGENETICS KNOWLEDGE BASEU01GM061374 · NIGMS · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO · 2000 to 2009
$24.0M
NIGMS NIH HHS U01 GM061374NIGMS NIH HHS U01 GM061393NIGMS NIH HHS UO1GM61374NIGMS NIH HHS UO1GM61393
6 · The paper itself

Abstract

Identifying heritable genetic variants responsible for chemotherapeutic toxicities has been challenging due in part to its multigenic nature. To date, there is a paucity of data on genetic variants associated with patients experiencing severe myelosuppression or cardiac toxicity following treatment with daunorubicin. We present a genome-wide model using International HapMap cell lines that integrate genotype and gene expression to identify genetic variants that contribute to daunorubicin-induced cytotoxicity. A cell growth inhibition assay was used to measure variations in the cytotoxicity of daunorubicin. Gene expression was determined using the Affymetrix GeneChip Human Exon 1.0ST Array. Using sequential analysis, we evaluated the associations between genotype and cytotoxicity, those significant genotypes with gene expression and correlated gene expression of the identified candidates with cytotoxicity. A total of 26, 9, and 18 genetic variants were identified to contribute to daunorubicin-induced cytotoxicity through their effect on 16, 9, and 36 gene expressions in the combined, Centre d' Etude du Polymorphisme Humain (CEPH), and Yoruban populations, respectively. Using 50 non-HapMap CEPH cell lines, single nucleotide polymorphisms generated through our model predicted 29% of the overall variation in daunorubicin sensitivity and the expression of CYP1B1 was significantly correlated with sensitivity to daunorubicin. In the CEPH validation set, rs120525235 and rs3750518 were significant predictors of transformed daunorubicin IC(50) (P = 0.005 and P = 0.0008, respectively), and rs1551315 trends toward significance (P = 0.089). This unbiased method can be used to elucidate genetic variants contributing to a wide range of cellular phenotypes.

Indexed as

Polymorphism, Single NucleotideAntibiotics, AntineoplasticAryl Hydrocarbon HydroxylasesCell Line, TumorCytochrome P-450 CYP1B1Cytochrome P-450 Enzyme SystemDaunorubicinDrug Resistance, NeoplasmGenetic LinkageGenetic Predisposition to DiseaseGenotypeHumansInhibitory Concentration 50NeoplasmsAntibiotics, AntineoplasticAryl Hydrocarbon HydroxylasesCYP1B1 protein, humanCytochrome P-450 CYP1B1Cytochrome P-450 Enzyme SystemDaunorubicin

Identifiers

PMID18451141
PMCPMC2714371
OpenAlexW2155388118

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.