ArticleBreast cancer research and treatment2014
Genetic heterogeneity beyond CYP2C8*3 does not explain differential sensitivity to paclitaxel-induced neuropathy.
Article in Breast cancer research and treatment, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Pharmacogenetics of taxane-induced neurotoxicity in breast cancer: Systematic review and meta-analysis.Clinical and translational science · 2022Pooled it
- Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance).Cancer medicine · 2016Pooled it
- Reproducibility of pharmacogenetics findings for paclitaxel in a heterogeneous population of patients with lung cancer.PloS one · 2019Trial
- Review of the contribution of clinical and genetic factors to the racial disparity in taxane-induced peripheral neuropathy.Critical reviews in oncology/hematology · 2025Review
- Strain-dependent neuronal disposition and toxicity of paclitaxel in mice.ASPET discovery · 2025Article
- The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment.Pharmaceutics · 2024Review
- Omics Technologies Improving Breast Cancer Research and Diagnostics.International journal of molecular sciences · 2023Review
- Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- Management of Side Effects in the Personalized Medicine Era: Chemotherapy-Induced Peripheral Neurotoxicity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Microtubule-Interfering Drugs: Current and Future Roles in Epithelial Ovarian Cancer Treatment.Cancers · 2021Review
- Genetic variants predictive of chemotherapy-induced peripheral neuropathy symptoms in gynecologic cancer survivors.Gynecologic oncology · 2021Article
- Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems.Experimental neurology · 2020Review
- Toxicity and Pharmacogenomic Biomarkers in Breast Cancer Chemotherapy.Frontiers in pharmacology · 2020Review
- Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2019Review
- Polymorphisms of CYP2C8 Alter First-Electron Transfer Kinetics and Increase Catalytic Uncoupling.International journal of molecular sciences · 2019Article
- Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.Pharmacogenomics · 2019Article
- Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results.Frontiers in pharmacology · 2017Article
- Systematic tracking of disrupted modules identifies significant genes and pathways in hepatocellular carcinoma.Oncology letters · 2016Article
- DMET™ (Drug Metabolism Enzymes and Transporters): a pharmacogenomic platform for precision medicine.Oncotarget · 2016Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
The development of paclitaxel-induced peripheral neuropathy (PIPN) is influenced by drug exposure and patient genetics. The purpose of this analysis was to expand on a previous reported association of CYP2C8*3 and PIPN risk by investigating additional polymorphisms in CYP2C8 and in hundreds of other genes potentially relevant to paclitaxel pharmacokinetics. Clinical data was collected prospectively in an observational registry of newly diagnosed breast cancer patients. Patients treated with paclitaxel-containing regimens were genotyped using the Affymetrix DMET™ Plus chip. Patients who carried the CYP2C8*2, *3, or *4 variant were collapsed into a low-metabolizer CYP2C8 phenotype for association with PIPN. Separately, all SNPs that surpassed quality control were assessed individually and as a composite of genetic ancestry for associations with PIPN. 412 paclitaxel-treated patients and 564 genetic markers were included in the analysis. The risk of PIPN was significantly greater in the CYP2C8 low-metabolizer group (HR = 1.722, p = 0.018); however, the influences of the *2 and *4 SNPs were not independently significant (*2: p = 0.847, *4: p = 0.408). One intronic SNP in ABCG1 (rs492338) surpassed the exploratory significance threshold for an association with PIPN in the Caucasian cohort (p = 0.0008) but not in the non-Caucasian replication group (p = 0.54). Substantial genetic variability was observed within self-reported racial groups but this genetic variability was not associated with risk of grade 2+ PIPN. The pharmacogenetic heterogeneity within a cohort of breast cancer patients is dramatic, though we did not find evidence that this heterogeneity directly influences the risk of PIPN beyond the contribution of CYP2C8*3.
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Registered trials
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