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An inherited genetic variant of the CEP72 gene is associated with the development of vincristine-induced peripheral neuropathy in female patients with aggressive B-cell lymphoma.

Authors :
Christofyllakis, Konstantinos
Kaddu-Mulindwa, Dominic
Lesan, Vadim
Rixecker, Torben
Kos, Igor Age
Held, Gerhard
Regitz, Evi
Pfreundschuh, Michael
Bittenbring, Joerg Thomas
Thurner, Lorenz
Poeschel, Viola
Ziepert, Marita
Altmann, Bettina
Bewarder, Moritz
Source :
Annals of Hematology. Nov2024, Vol. 103 Issue 11, p4599-4606. 8p.
Publication Year :
2024

Abstract

Vincristine-induced peripheral neuropathy (VIPN) is an adverse effect of regimens used for the treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL). A single-nucleotide polymorphism (SNP) in the promotor region of the CEP72 gene has been identified as risk factor for the development of VIPN in children. To validate these results in adults we aimed to determine the association of the high-risk CEP72 (rs924607 TT genotype) with the occurrence and severity of VIPN. Analysis of SNP rs924607 (TT, CC or CT) was performed in all enrolled patients with available blood samples with a TaqMan genotyping assay. Rates and grades of VIPN were assessed prospectively as part of the RICOVER-60 trial. CEP72 genotype could be assessed in 519 patients. VIPN data was available for 499/519 patients who were included in the final analysis. 286 (57%) patients developed VIPN of any grade during treatment. Grade 2–4 VIPN occurred in 33% (166/499) of patients. The high-risk CEP72 TT genotype at rs924607 was identified in 97/499 (19%) patients. The TT genotype was not correlated with VIPN in the overall study population compared to patients with either CC or CT genotypes (p = 0.748). However, in the subgroup of female patients, the TT genotype was associated with increased occurrence of any-grade VIPN as well as grade 2–4 VIPN as compared to patients with either CC or CT genotypes (p = 0.016 and p = 0.020, respectively). Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09395555
Volume :
103
Issue :
11
Database :
Academic Search Index
Journal :
Annals of Hematology
Publication Type :
Academic Journal
Accession number :
180653960
Full Text :
https://doi.org/10.1007/s00277-024-05973-9