Pharmacogenomic Predictors of Induced Peripheral Neuropathy in Cancer Patients: A Systematic Review and Meta-analysis
Isabella Barretto1, Francisco de Moraes2, João Zorzatto1, Nayara Moretti1, Pedro Bartkevitch3, Mario Hirata4
1School of Medicine, University of Western São Paulo, 2Federal University of Pará, 3Department of Neurosurgery, Miller School of Medicine, University of Miami, 4University of Sao Paulo
Objective:
Identify pharmacogenomic variants associated with vincristine-induced peripheral neuropathy (VIPN) and to quantify their impact on VIPN risk through systematic review and meta-analysis.
Background:
Vincristine (VCR), a vinca alkaloid, is a critical component of combination chemotherapy for cancers such as leukemia and lymphoma. However, its clinical utility is severely limited by vincristine-induced peripheral neuropathy (VIPN), a dose-dependent neurotoxicity. Since susceptibility varies widely among individuals, the presence of genetic variants (single nucleotide polymorphisms - SNPs) in genes related to vincristine pharmacokinetics and pharmacodynamics has emerged as a key factor influencing VIPN risk.
Design/Methods:
A systematic search following PRISMA guidelines was conducted in PubMed, Scopus and Web of Science to identify studies on the association between genetic variants (polymorphisms) and the risk or severity of Vincristine-Induced Peripheral Neuropathy (VIPN) in cancer patients. Odds ratios (OR) with 95% confidence intervals (CI) was estimated using a random-effects model in RStudio version 4.2.3, with heterogeneity assessed by the I² statistic, with p < 0.05 considered significant.
Results:
Twenty-four studies were included. miR-4481 (rs7896283) was associated with increased VIPN risk (OR: 2.16, 95% CI: 1.17–3.99; I² = 73.0%), as was CEP72 (rs924607) (OR: 1.96, 95% CI: 1.59–2.42; I² = 59.6%). CYP3A5 (rs776746) showed a nonsignificant trend (OR: 2.09, 95% CI: 0.97–4.51; I² = 29.2%). MTNR1B (rs12786200) (OR: 0.31, 95% CI: 0.19–0.49; I² = 41.7%) and miR-124-1 (rs12402181) (OR: 0.26, 95% CI: 0.11–0.61; I² = 43.1%) were associated with reduced VIPN risk.
Conclusions:
miR-4481 and CEP72 polymorphisms were significantly associated with increased VIPN risk, whereas MTNR1B and miR-124-1 variants were linked to reduced risk. CYP3A5 showed a nonsignificant trend toward higher VIPN susceptibility. These findings suggest that genetic variations in genes involved in vincristine pharmacokinetics and pharmacodynamics may influence neurotoxicity risk, highlighting the potential of pharmacogenomic profiling to personalize chemotherapy and minimize adverse effects.
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