Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy

Paclitaxel is a microtubule-binding drug widely used to treat several solid tumors. The paclitaxel dose-limiting toxicity is peripheral neuropathy, which is dose-cumulative and occurs in about one third of the patients. It exhibits a large interindividual variability of unknown molecular basis. We have conducted a GWAS in patients uniformly treated with paclitaxel/carboplatin by which we independently support EPHA5-rs7349683 and XKR4-rs4737264 as markers of paclitaxel-induced neuropathy. In addition, other EPHA genes, also involved in axonal guidance and repair following neural injury, as well as LIMK2 locus, may play an important role in the development of this toxicity. The identified SNPs could form the basis for individualized paclitaxel chemotherapy. (By Luis Javier Leandro García, http://jmg.bmj.com/content/early/2013/06/16/jmedgenet-2012-101466 )