ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Regulatory polymorphisms in β-tubulin IIa are associated with paclitaxel-induced peripheral neuropathy.
Article 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. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Pharmacogenetics of taxane-induced neurotoxicity in breast cancer: Systematic review and meta-analysis.Clinical and translational science · 2022Pooled it
- Charcot-Marie-Tooth gene, SBF2, associated with taxane-induced peripheral neuropathy in African Americans.Oncotarget · 2016Trial
- Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients.British journal of cancer · 2016Trial
- Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).The pharmacogenomics journal · 2014Trial
- Time‑resolved multi-omic analysis of paclitaxel exposure in human iPSC‑derived sensory neurons unveils mechanisms of chemotherapy‑induced peripheral neuropathy.Cell death & disease · 2026Article
- Review of the contribution of clinical and genetic factors to the racial disparity in taxane-induced peripheral neuropathy.Critical reviews in oncology/hematology · 2025Review
- Role of tubulin post-translational modifications in peripheral neuropathy.Experimental neurology · 2023Review
- Uncovering potential diagnostic biomarkers of acute myocardial infarction based on machine learning and analyzing its relationship with immune cells.BMC cardiovascular disorders · 2023Article
- Mechanistic insights into the pathogenesis of microtubule-targeting agent-induced peripheral neuropathy from pharmacogenetic and functional studies.Basic & clinical pharmacology & toxicology · 2022Review
- The impact of SBF2 on taxane-induced peripheral neuropathy.PLoS genetics · 2022Article
- Microtubule-Interfering Drugs: Current and Future Roles in Epithelial Ovarian Cancer Treatment.Cancers · 2021Review
- Chemotherapy and peripheral neuropathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets.Clinical pharmacology and therapeutics · 2021Article
- Article
- Exploring pharmacogenetics of paclitaxel- and docetaxel-induced peripheral neuropathy by evaluating the direct pharmacogenetic-pharmacokinetic and pharmacokinetic-neuropathy relationships.Expert opinion on drug metabolism & toxicology · 2021Review
- Pathogenic role of delta 2 tubulin in bortezomib-induced peripheral neuropathy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Plasma polymerized nanoparticles effectively deliver dual siRNA and drug therapy in vivo.Scientific reports · 2020Article
- 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
- Role of Germline Genetics in Identifying Survivors at Risk for Adverse Effects of Cancer Treatment.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2018Review
- Supplement Use and Chemotherapy-Induced Peripheral Neuropathy in a Cooperative Group Trial (S0221): The DELCaP Study.Journal of the National Cancer Institute · 2017Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
purposePeripheral neuropathy is the dose-limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat several solid tumors such as breast, lung, and ovary. The cytotoxic effect of paclitaxel is mediated through β-tubulin binding in the cellular microtubules. In this study, we investigated the association between paclitaxel neurotoxicity risk and regulatory genetic variants in β-tubulin genes. EXPERIMENTAL
designWe measured variation in gene expression of three β-tubulin isotypes (I, IVb, and IIa) in lymphocytes from 100 healthy volunteers, sequenced the promoter region to identify polymorphisms putatively influencing gene expression and assessed the transcription rate of the identified variants using luciferase assays. To determine whether the identified regulatory polymorphisms were associated with paclitaxel neurotoxicity, we genotyped them in 214 patients treated with paclitaxel. In addition, paclitaxel-induced cytotoxicity in lymphoblastoid cell lines was compared with β-tubulin expression as measured by Affymetrix exon array.
resultsWe found a 63-fold variation in β-tubulin IIa gene (TUBB2A) mRNA content and three polymorphisms located at -101, -112, and -157 in TUBB2A promoter correlated with increased mRNA levels. The -101 and -112 variants, in total linkage disequilibrium, conferred TUBB2A increased transcription rate. Furthermore, these variants protected from paclitaxel-induced peripheral neuropathy [HR, 0.62; 95% confidence interval (CI), 0.42-0.93; P = 0.021, multivariable analysis]. In addition, an inverse correlation between TUBB2A and paclitaxel-induced apoptosis (P = 0.001) in lymphoblastoid cell lines further supported that higher TUBB2A gene expression conferred lower paclitaxel sensitivity.
conclusionsThis is the first study showing that paclitaxel neuropathy risk is influenced by polymorphisms regulating the expression of a β-tubulin gene.
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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.