ABCC2 Genetic Variation and Vincristine-Induced Peripheral Neuropathy Risk in Mexican Pediatric Patients with Acute Lymphoblastic Leukemia
Year: 2026
Type: article
Abstract: Vincristine-induced peripheral neuropathy (VIPN) is a common dose-limiting toxicity in pediatric acute lymphoblastic leukemia (ALL), and pharmacogenetic evidence in admixed populations remains limited. We evaluated variants in ABCC1, ABCC2, ABCB1, CYP3A4, CYP3A5, and CEP72 in Mexican pediatric patients with ALL using an ambispective case–control design (n = 43; aged 2–18 years). VIPN was graded using CTCAE v4.0; cases were defined as grade ≥ 2 (n = 11) and controls grade 0–1 (n = 32). Nine single nucleotide variants (SNVs) were genotyped by allele-specific qPCR and analyzed under codominant, dominant, recessive, and log-additive models, including haplotype analyses. VIPN occurred in 25.6% of patients, with 90.9% of cases occurring during induction (p = 0.001). ABCC2 rs11190298 was nominally associated with VIPN under codominant (OR = 0.21; 95% CI: 0.04–0.97), dominant (OR = 0.15; 95% CI: 0.03–0.71), and log-additive (OR = 0.17; 95% CI: 0.04–0.66) models, and ABCC2 haplotypes showed a nominal global association (p = 0.003). These associations did not withstand correction for multiple testing. No significant associations were found for ABCC1, ABCB1, CYP3A4, CYP3A5, or CEP72. Early-onset toxicity may reflect differences in drug exposure or treatment intensity, which pharmacokinetic data could clarify. These hypothesis-generating findings require replication in larger prospective cohorts.
DOI: 10.3390/ijms27219998
Institutions: Instituto Politécnico Nacional, Secretaria de Salud
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225649822