Abstract:
: Vincristine-induced peripheral neuropathy (VIPN) is a debilitating side-effect of vincristine.
It remains a challenge to predict which patients will suffer from VIPN. Pharmacogenomics may
explain an individuals’ susceptibility to side-effects. In this systematic review and meta-analysis, we
describe the influence of pharmacogenomic parameters on the development of VIPN in children with
cancer. PubMed, Embase and Web of Science were searched. In total, 1597 records were identified
and 21 studies were included. A random-effects meta-analysis was performed for the influence
of CYP3A5 expression on the development of VIPN. Single-nucleotide polymorphisms (SNPs) in
transporter-, metabolism-, cytoskeleton-, and hereditary neuropathy-associated genes and SNPs
in genes previously unrelated to vincristine or neuropathy were associated with VIPN. CYP3A5
expression status was not significantly associated with VIPN. The comparison and interpretation
of the results of the included studies was limited due to heterogeneity in the study population,
treatment protocol and assessment methods and definitions of VIPN. Independent replication is
essential to validate the clinical significance of the reported associations. Future research should aim
for prospective VIPN assessment in both a discovery and a replication cohort. Ultimately, the goal
would be to screen patients upfront to determine optimal vincristine dosage with regards to efficacy
and risk of VIPN.