Polymorphic variants in NR1I3 and UGT2B7 predict taxane neurotoxicity and have prognostic relevance in breast cancer patients: a case-control study

Taxane-related peripheral neuropathy (TrPN) is a dose-limiting toxicity with important inter-individual variability. Genetic polymorphisms in ADME genes may account for variability in drug efficacy and/or toxicity. By the use of Affymetrix DMETTM microarray platform, in a retrospective case-control study, the correlation between ADME polymorphic variants and grade >=2-3 TrPN (G>=2-3 TrPN) was investigated. In a breast cancer (BC) training set, 5 SNPs in NR1I3 and UGT2B7genes were correlated to G>=2-3-TrPN protection. By ROC curves, the G>=2-3-TrPN-related candidate biomarkers in an independent series of 54 BC patients (17 cases and 37 controls) were validated. NR1I3 was correlated to Paclitaxel-TrPN and UGT2B7 to Docetaxel-TrPN. Moreover, a genetic signature of prognostic relevance for BC outcome was found. Our findings might have potential relevance for personalized management of BC patients for prevention of treatment failure in ultrametabolizer genetic variants.