ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Why pharmacogenomic biomarkers for chemotherapy-induced peripheral neuropathy fail: a systematic review of genetic associations, replication, and clinical translation.Frontiers in pharmacology · 2026Pooled it
- A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma.Haematologica · 2019Trial
- Genetic architecture of multiple myeloma: From somatic alterations to germline susceptibility and clinical implications.Translational oncology · 2026Review
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- Multiple myeloma.Nature reviews. Disease primers · 2024Review
- A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients.Oncology research · 2024Article
- Bortezomib induced peripheral neuropathy and single nucleotide polymorphisms in PKNOX1.Biomarker research · 2023Article
- Management of Side Effects in the Personalized Medicine Era: Chemotherapy-Induced Peripheral Neurotoxicity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The Relationship ofJournal of clinical medicine · 2021Article
- Hydrogen sulfide in ageing, longevity and disease.The Biochemical journal · 2021Review
- Chemotherapy and peripheral neuropathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.International journal of molecular sciences · 2021Review
- DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma.Clinical epigenetics · 2020Article
- Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.Cancers · 2020Article
- Views on GWAS statistical analysis.Bioinformation · 2020Article
- Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma.Cancer science · 2019Article
- 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
- Model-based clustering for identifying disease-associated SNPs in case-control genome-wide association studies.Scientific reports · 2019Article
- Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.International journal of molecular sciences · 2019Review
- Alterations of 63 hub genes during lingual carcinogenesis in C57BL/6J mice.Scientific reports · 2018Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
purposePainful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity. EXPERIMENTAL
designA genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk variants for developing severe bortezomib-induced peripheral neuropathy (BiPN) in 469 patients with multiple myeloma who received bortezomib-dexamethasone therapy prior to autologous stem cell in randomized clinical trials of the Intergroupe Francophone du Myelome (IFM) and findings were replicated in 114 patients with multiple myeloma of the HOVON-65/GMMG-HD4 clinical trial.
resultsAn SNP in the PKNOX1 gene was associated with BiPN in the exploratory cohort [rs2839629; OR, 1.89, 95% confidence interval (CI), 1.45-2.44; P = 7.6 × 10(-6)] and in the replication cohort (OR, 2.04; 95% CI, = 1.11-3.33; P = 8.3 × 10(-3)). In addition, rs2839629 is in strong linkage disequilibrium (r(2) = 0.87) with rs915854, located in the intergenic region between PKNOX1 and cystathionine-ß-synthetase (CBS) Expression quantitative trait loci mapping showed that both rs2839629 and rs915854 genotypes have an impact on PKNOX1 expression in nerve tissue, whereas rs2839629 affects CBS expression in skin and blood.
conclusionsThe use of GWAS in multiple myeloma pharmacogenomics has identified a novel candidate genetic locus mapping to PKNOX1 and in the immediate vicinity of CBS at 21q22.3 associated with the severe bortezomib-induced toxicity. The proximity of these two genes involved in neurologic pain whose tissue-specific expression is modified by the two variants provides new targets for neuroprotective strategies. Clin Cancer Res; 22(17); 4350-5. ©2016 AACR.
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