Charcot-Marie-Tooth gene, SBF2, associated with taxane-induced peripheral neuropathy in African Americans

// Bryan P. Schneider 1,* , Dongbing Lai 1,* , Fei Shen 1,* , Guanglong Jiang 1 , Milan Radovich 1 , Lang Li 1 , Laura Gardner 1 , Kathy D. Miller 1 , Anne O’Neill 2 , Joseph A. Sparano 3 , Gloria Xue 1 , Tatiana Foroud 1,** and George W. Sledge Jr. 4,** 1 Indiana University School of Medicine, Indianapolis, Indiana, USA 2 Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, Massachusetts, USA 3 Albert Einstein University, Montefiore Medical Center, Bronx, New York, USA 4 Stanford University School of Medicine, Stanford, California, USA * These authors have contributed equally to this work ** These authors have contributed equally to this work Correspondence to: Bryan P. Schneider, email: // Keywords : whole exome sequencing, African American, paclitaxel, peripheral neuropathy, SBF2 Received : August 29, 2016 Accepted : September 18, 2016 Published : October 09, 2016 Abstract Purpose: Taxane-induced peripheral neuropathy (TIPN) is one of the most important survivorship issues for cancer patients. African Americans (AA) have previously been shown to have an increased risk for this toxicity. Germline predictive biomarkers were evaluated to help identify a priori which patients might be at extraordinarily high risk for this toxicity. Experimental design: Whole exome sequencing was performed using germline DNA from 213 AA patients who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Cases were defined as those with either grade 3-4 (n=64) or grade 2-4 (n=151) TIPN and were compared to controls (n=62) that were not reported to have experienced TIPN. We retained for analysis rare variants with a minor allele frequency