Wright, Galen E BGalen E BWrightAmstutz, UrsulaUrsulaAmstutzDrögemöller, Britt IBritt IDrögemöllerShih, JoanneJoanneShihRassekh, Shahrad RShahrad RRassekhHayden, Michael RMichael RHaydenCarleton, Bruce CBruce CCarletonRoss, Colin J DColin J DRoss2024-10-082024-10-082019-02https://boris-portal.unibe.ch/handle/20.500.12422/63726Vincristine 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, CEP72 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. CEP72 rs924607 was significantly associated with VIPN (P = 0.02; odds ratio (OR) = 3.4). ADME analyses identified associations between VIPN and ABCC1 rs3784867 (P = 5.34 × 10 ; OR = 4.9), and SLC5A7 rs1013940 (P = 9.00 × 10 ; 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 ; OR = 2.0), a heritable neuropathy-related gene. This study provides essential corroboratory evidence for CEP72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.1258062999951610.1002/cpt.1179