Leveraging GWAS Data Derived From a Large Cooperative Group Trial to Identify a SNP Cluster Associated With the Risk of Taxane-induced Peripheral Neuropathy

Abstract BackgroundChemotherapy-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 analytic to describe taxane-associated CIPN risk.MethodsWe analyzed GWAS data derived from ECOG-5103, first identifying SNPs that were most strongly associated with CIPN using Fisher’s ratio. We then ranked ordered those SNPs which discriminated CIPN-positive 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).ResultsUsing GWAS aggregate data, we identified a 267 SNP cluster which was associated with a CIPN+ phenotype with an accuracy of 96.1%. ConclusionsIdentification of a 267 SNP cluster could accurately predict CIPN risk. Validation using an independent patient cohort should be performed.