Association of the Charcot–Marie–Tooth disease gene ARHGEF10 with paclitaxel induced peripheral neuropathy in NCCTG N08CA (Alliance)

摘要: Abstract The predisposition of patients to develop polyneuropathy in response toxic exposure may have a genetic basis. previous study Alliance N08C1 found an association the Charcot–Marie–Tooth disease (CMT) gene ARHGEF10 with paclitaxel chemotherapy induced peripheral neuropathy (CIPN) related three non-synonymous, recurrent single nucleotide variants (SNV), whereby rs9657362 had strongest effect, and rs2294039 rs17683288 contributed only weakly. In present report, N08CA was chosen attempt replicate above finding. because it is methodologically most similar (to N08C1) performed CIPN field date. enrolled receiving neurotoxic agent paclitaxel. Polyneuropathy assessed by serial repeat administration previously validated patient reported outcome instrument CIPN20. A study-wide, Rasch type model used perform extreme phenotyping n = 138 eligible from which “cases” “controls” were selected for analysis SNV TaqMan PCR. significant under pre-specified primary endpoint, significance level p = 0.024. As original study, seen (odds ratio = 3.56, p = 0.018). To further compare results across new statistical “classifier” tested, achieved ROC area curve 0.60 0.66 N08C1, demonstrating good agreement. Retesting endpoint replication CIPN.