Evidence map›Paper›PMID 22843789›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2012

A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101.

R Michael Baldwin, Kouros Owzar, Hitoshi Zembutsu, Aparna Chhibber, Michiaki Kubo, Chen Jiang, Dorothy Watson, Rachel J Eclov, Joel Mefford, Howard L McLeod and 9 more

2 registry-linked trialsAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 112 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 7 pooled it
9.7field-weighted citation impact, top 1% 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.

NCT00041119 phase3completednot on this map

Cyclophosphamide And Doxorubicin (CA) (4 VS 6 Cycles) Versus Paclitaxel (4 VS 6 Cycles) As Adjuvant Therapy For Breast Cancer in Women With 0-3 Positive Axillary Lymph Nodes:A 2X2 Factorial Phase III Randomized Study

TypeinterventionalSponsorAlliance for Clinical Trials in OncologyRan2002 to 2014Enrolled3,871ConditionsBreast CancerArmsAC regimen, cyclophosphamide, doxorubicin hydrochloride, paclitaxel
NCT02864030 phase4completednot on this mapstarted 2014, after this paper: background citation

Multicenter, Interventional, Single-arm, Phase IV Study Evaluating Tolerability of Eribulin and Its Relationship With a Set of Polymorphisms in an Unselected Population of Female Patients With Metastatic Breast Cancer

TypeinterventionalSponsorOncologia Medica dell'Ospedale FatebenefratelliRan2014 to 2020Enrolled200ConditionsMetastatic Breast Cancer, Toxicity, Neurotoxicity, Drug ToxicityArmsERIBULIN MESYLATE
3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 7 syntheses or guidelines pooled it, 204 citations in OpenAlex.

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52 more citing papers are in PubMed but not listed here.

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

19 authors at 7 institutions in 2 countries.

R Michael BaldwinDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th Street RH584E, San Francisco, CA 94158-2911, USA.
Kouros Owzar
Hitoshi Zembutsu
Aparna Chhibber
Michiaki Kubo
Chen Jiang
Dorothy Watson
Rachel J Eclov
Joel Mefford
Howard L McLeod
Paula N Friedman
Clifford A Hudis
Eric P Winer
Eric M Jorgenson
John S Witte
Lawrence N Shulman
Yusuke Nakamura
Mark J Ratain
Deanna L Kroetz
The University of Tokyo · JPDana-Farber Cancer Institute · USDuke University · USMemorial Sloan Kettering Cancer Center · USUniversity of California, San Francisco · USUniversity of Chicago · USRIKEN Center for Integrative Medical Sciences · JP

Funding

CANCER AND LEUKEMIA GROUP B MINORITY SATELLITE SUPPLEMENU10CA031946 · NCI · UNIVERSITY OF CHICAGO · PI BERTAGNOLLI, MONICA M · 1985 to 2013
$158.4M
CANCER &LEUKEMIA GROUP B STATISTICAL CENTERU10CA033601 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SARGENT, DANIEL J. · 1985 to 2013
$69.4M
Whole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI RATAIN, MARK J · 2000 to 2014
$39.0M
PHARMACOGENETICS OF MEMBRANE TRANSPORTERSU01GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GIACOMINI, KATHLEEN M · 2000 to 2009
$29.2M
Statistical Methods for Cancer Clinical TrialsP01CA142538 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KOSOROK, MICHAEL R · 2010 to 2019
$21.3M
Pharmacogenomics of Membrane TransportersU19GM061390 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KWOK, PUI-YAN · 2010 to 2014
$16.3M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
NCI NIH HHS CA31946NCI NIH HHS CA33601NCI NIH HHS P01 CA142538NCI NIH HHS U10 CA031946NCI NIH HHS U10 CA033601NIGMS NIH HHS GM61390NIGMS NIH HHS GM61393NIGMS NIH HHS T32 GM007175NIGMS NIH HHS U01 GM061390NIGMS NIH HHS U01 GM061393NIGMS NIH HHS U19 GM061390
6 · The paper itself

Abstract

purposeSensory peripheral neuropathy is a common and sometimes debilitating toxicity associated with paclitaxel therapy. This study aims to identify genetic risk factors for the development of this toxicity. EXPERIMENTAL

designA prospective pharmacogenetic analysis of patients with primary breast cancer, randomized to the paclitaxel arm of CALGB 40101, was used to identify genetic predictors of the onset and severity of sensory peripheral neuropathy. A genome-wide association study in 855 subjects of European ancestry was conducted and findings were replicated in additional European (n = 154) and African American (n = 117) subjects.

resultsA single nucleotide polymorphism in FGD4 was associated with the onset of sensory peripheral neuropathy in the discovery cohort [rs10771973; HR, 1.57; 95% confidence interval (CI), 1.30-1.91; P = 2.6 × 10(-6)] and in a European (HR, 1.72; 95% CI, 1.06-2.80; P = 0.013) and African American (HR, 1.93; 95% CI, 1.13-3.28; P = 6.7 × 10(-3)) replication cohort. There is also evidence that markers in additional genes, including EPHA5 (rs7349683) and FZD3 (rs10771973), were associated with the onset or severity of paclitaxel-induced sensory peripheral neuropathy.

conclusionsA genome-wide association study has identified novel genetic markers of paclitaxel-induced sensory peripheral neuropathy, including a common polymorphism in FGD4, a congenital peripheral neuropathy gene. These findings suggest that genetic variation may contribute to variation in development of this toxicity. Validation of these findings may allow for the identification of patients at increased risk of peripheral neuropathy and inform the use of an alternative to paclitaxel and/or the clinical management of this toxicity.

Indexed as

Genetic Predisposition to DiseaseAdultAgedAntineoplastic Agents, PhytogenicBreast NeoplasmsFemaleGenetic LociGenome-Wide Association StudyGenotypeHumansIncidenceMicrofilament ProteinsMiddle AgedPaclitaxelPeripheral Nervous System DiseasesPolymorphism, Single NucleotideAntineoplastic Agents, PhytogenicFGD4 protein, humanMicrofilament ProteinsPaclitaxelReceptor, EphA5

Identifiers

PMID22843789
PMCPMC3445665
OpenAlexW2169311890

What OpenQuestion holds

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Registered trials

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.