Identification of a SNP cluster associated with taxane-induced peripheral neuropathy risk in patients being treated for breast cancer using GWAS data derived from a large cooperative group trial.
Support Care Cancer
; 31(2): 139, 2023 Jan 28.
Article
em En
| MEDLINE
| ID: mdl-36707490
ABSTRACT
BACKGROUND:
Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity of taxanes for which there is no effective intervention. Genomic CIPN risk determination has yielded promising, but inconsistent results. The present study assessed the utility of a collective SNP cluster identified using novel analytics to describe taxane-associated CIPN risk.METHODS:
We analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher's ratio (FR). We then ranked ordered those SNPs which discriminated CIPN-positive (CIPN +) from CIPN-negative phenotypes based on their discriminatory power and developed the cluster of SNPs which provided the highest predictive accuracy using leave-one-out cross-validation (LOOCV).RESULTS:
Using aggregated genotype data obtained from the previously reported ECOG-5103 clinical trial (in which two different arrays were used, HumanOmniExpress (727,227 SNPs) and HumanOmni1-Quad1 (1,131,857 SNPs)), we identified a 267 SNP cluster which was associated with a CIPN + phenotype with an accuracy of 96.1%.CONCLUSIONS:
A cluster of SNPs was identified which prospectively discriminated patients most likely to develop symptomatic CIPN following taxane exposure as part of a breast cancer chemotherapy regimen. Validation using an independent patient cohort should be performed.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Doenças do Sistema Nervoso Periférico
/
Taxoides
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Support Care Cancer
Assunto da revista:
NEOPLASIAS
/
SERVICOS DE SAUDE
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos