Genetic determinants of chronic oxaliplatin-induced peripheral neurotoxicity: a genome-wide study replication and meta-analysis.
J Peripher Nerv Syst
; 20(1): 15-23, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25858589
ABSTRACT
We aimed at validating the role of genetic variants identified by a recent genome-wide association study (GWAS) as determinants of chronic oxaliplatin-induced peripheral neurotoxicity (OXAIPN). Eight polymorphisms (rs10486003, rs2338, rs843748, rs797519, rs4936453, rs12023000, rs17140129, and rs6924717) were genotyped in a total of 150 colorectal cancer patients of Caucasian origin receiving oxaliplatin-based chemotherapy. The severity grade of chronic OXAIPN was assessed by NCI-CTC criteria and the clinical version of the Total Neuropathy Score(©) (TNSc(©) ). None of the polymorphisms investigated was found associated with grade ≥ 2 chronic OXAIPN (NCI-CTC criteria), while a nominal association emerged for ACYP2 rs843748 when using the TNSc(©) scale (dominant model odds ratio [OR] 0.27, 95% confidence interval [CI] 0.10-0.75, P = 0.008). In the combined analysis of this results with data of the two previously published studies which assessed chronic OXAIPN by NCI-CTC criteria, evidence suggestive of association with chronic OXAIPN (NCI-CTC criteria) was found for ACYP2 rs843748 (dominant model OR 2.40, 95%CI 1.40-5.24, P = 0.027), which, however, did not remain significant after correction for multiple testing (threshold P-value <0.00625). These findings suggest a minor role of the single nucleotide polymorphisms (SNPs) investigated as genetic determinants of chronic OXAIPN. These results also highlight the importance of replication studies with meta-analysis for validation of GWAS findings.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
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Hidrolases Anidrido Ácido
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Doenças do Sistema Nervoso Periférico
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Polimorfismo de Nucleotídeo Único
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
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Systematic_reviews
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Peripher Nerv Syst
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália