Contribution of common and rare genetic variants in CEP72 on vincristine-induced peripheral neuropathy in brain tumour patients.
Br J Clin Pharmacol
; 88(7): 3463-3473, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35150001
ABSTRACT
AIMS:
Studies implicated a role for a genetic variant in CEP72 in vincristine-induced peripheral neuropathy. This study aims to evaluate this association in a cohort of brain tumour patients, to perform a cross-disease meta-analysis and explore the protein-coding region of CEP72.METHODS:
In total, 104 vincristine-treated brain tumour patients were genotyped for CEP72 rs924607, and sequenced for the protein-coding region. Data regarding patient and treatment characteristics, and peripheral neuropathy, were collected. Logistic regression and meta-analysis were performed for rs924607 replication. A weighted burden analysis was applied to evaluate impact of overall genetic variation in CEP72.RESULTS:
Analysis of 24 cases and 80 controls did not show a significant association between CEP72 rs924607 and neuropathy (odds ratio, OR [95% confidence interval, CI] 2.076 [0.359-11.989], P = .414). When combined with 8 cohorts (1095 cancer patients), a significant increase in risk for neuropathy was found for patients with a TT genotype (OR [95% CI] 2.15 [1.35-3.43], P = .001). Additionally, a missense variant (rs12522955) was significantly associated (OR [95% CI] 2.3 [1.2-4.4], P = .041) and patients with severe neuropathy carried more impactful variants in CEP72 coding regions (P = .039).CONCLUSION:
The association of CEP72 rs924607 in vincristine-induced neuropathy was not confirmed in a cohort of brain tumour patients, but did contribute to its suggested effect when combined in a cross-disease meta-analysis. The importance of other genetic variations in CEP72 on vincristine-induced neuropathy was demonstrated. This study contributes to evidence of the importance of genetic variants in CEP72 in development of vincristine-induced toxicity, and provides guidance for future prospective studies.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Doenças do Sistema Nervoso Periférico
Tipo de estudo:
Guideline
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Observational_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article