ABCC2 Genetic Variation and Vincristine-Induced Peripheral Neuropathy Risk in Mexican Pediatric Patients with Acute Lymphoblastic Leukemia
- 1Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional Unidad Durango (CIIDIR Durango), Instituto Politécnico Nacional, Durango 34220, Durango, Mexico
- 2Centro Estatal de Cancerología de Durango (CECAN), Secretaria de Salud del Estado de Durango, Durango 34000, Durango, Mexico
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.
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BibTeX
@article{monroybaroja2026abcc2,
title = {{ABCC2 Genetic Variation and Vincristine-Induced Peripheral Neuropathy Risk in Mexican Pediatric Patients with Acute Lymphoblastic Leukemia}},
author = {María Fernanda Monroy-Baroja and Carlos Galaviz-Hernandez and Laura María García-Torres and Elio Aarón Reyes-Espinoza and Luis Felipe Cuellar-Guzman and Lourdes Patricia Córdova-Hurtado and Laura Jazel Barragan-Zuñiga and Martha Sosa-Macías},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219998},
url = {https://www.mdpi.com/1422-0067/27/21/9998},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ABCC2 Genetic Variation and Vincristine-Induced Peripheral Neuropathy Risk in Mexican Pediatric Patients with Acute Lymphoblastic Leukemia
AU - María Fernanda Monroy-Baroja
AU - Carlos Galaviz-Hernandez
AU - Laura María García-Torres
AU - Elio Aarón Reyes-Espinoza
AU - Luis Felipe Cuellar-Guzman
AU - Lourdes Patricia Córdova-Hurtado
AU - Laura Jazel Barragan-Zuñiga
AU - Martha Sosa-Macías
PY - 2026
DA - 2026/11/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219998
UR - https://www.mdpi.com/1422-0067/27/21/9998
AB - 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.
SN - 1422-0067
ER -