Paclitaxel-Induced Severe Sensory Peripheral Neuropathy Is Associated With Ndrg-1 Genetic Variant And Negative Ndrg-1 Expression In Nerve Tissue

1054 Background: N-myc downstream regulated gene (NDRG)-1 has been implicated in Charcot Marie Tooth disease, a peripheral nerve hereditary disorder and in the development and maintenance of the myelin sheath. We hypothesize that NDRG-1 may be implicated in paclitaxel-induced peripheral neuropathy. Methods: Breast cancer patients who received adjuvant weekly paclitaxel were genotyped for 10 single nucleotide polymorphisms (SNPs) in 9 genes, including rs2233335 in NDRG-1 using MassArray (Sequenom) technology. Immunohistochemical (IHC) staining of NDRG-1 was performed on normal nerve tissue in archival lumpectomy/mastectomy specimens. Clinical data including paclitaxel dose intensity and density, onset and severity of neuropathy was correlated with genetic and IHC data. Results: Of the 122 patients that were evaluated, 67% were Chinese, median age was 51 (26 – 79) years and 9% had diabetes. Mean total paclitaxel dose administered was 924 (240 – 960) mg/m2. Median duration of treatment was 12 (3 – 18) weeks,...