Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes

Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia ( ALL ). Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies ( VIPN ). We sought to determine the association of VIPN with a recently identified risk variant, CEP 72 rs924607, and drug absorption, distribution, metabolism, and excretion ( ADME ) gene variants in pediatric ALL . This was followed by a meta‐analysis of pharmacogenomic data from over 500 patients. CEP 72 rs924607 was significantly associated with VIPN ( P = 0.02; odds ratio ( OR ) = 3.4). ADME analyses identified associations between VIPN and ABCC 1 rs3784867 ( P = 5.34 × 10 −5 ; OR = 4.9), and SLC 5A7 rs1013940 ( P = 9.00 × 10 −4 ; OR = 8.6); genes involved in vincristine transport and inherited neuropathies, respectively. Meta‐analysis identified an association with a variant related to TTPA (rs10504361: P = 6.85 × 10 −4 ; OR = 2.0), a heritable neuropathy‐related gene. This study provides essential corroboratory evidence for CEP 72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN .