Journal Article

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers

Pérez-De Marcos, Juan Carlos, Cárdenas-Cardós, Rocío, Salinas-Lara, Citlaltepetl, Torres-Espíndola, Luz María, De Uña-Flores, Armando, Velasco-Hidalgo, Liliana, Castillejos-López, Manuel, Caballero-Salazar, Silvia, Fernández-Plata, Rosario, Aquíno-Gálvez, Arnoldo

2024

Overview

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098–5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74–35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87–16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915–16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83–15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747–11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831–22.02, p = 0.004, HR = 9.571, 95% CI 2.856–32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669–16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411–13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

• Publisher: MDPI AG
• Subject: ABCG2 gene / Adolescent / Antineoplastic drugs / ATP Binding Cassette Transporter, Subfamily B - genetics / ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics / Biomarkers, Tumor - genetics / Cancer / Cancer therapies / cancer therapy / Central nervous system / Central Nervous System Neoplasms - genetics / Central Nervous System Neoplasms - mortality / Central Nervous System Neoplasms - pathology / Chemotherapy / Child / Child mortality / Child, Preschool / Children / Cohort Studies / death / Development and progression / Drug resistance in microorganisms / drug therapy / Drug withdrawal / Drugs / Female / Genes / Genetic diversity / Genetic markers / Genetic Markers - genetics / Genetic testing / Genotype & phenotype / Health aspects / Humans / Infant / Lymphoma / Male / Medical prognosis / Mexico / Mortality / Multidrug resistance / Multidrug Resistance-Associated Protein 2 / Multidrug Resistance-Associated Proteins - genetics / multiple drug resistance / Neoplasm Proteins - genetics / Nervous system / Nervous system tumors / Nilotinib / Oncology / Patients / Pediatrics / Polymorphism, Single Nucleotide / quantitative polymerase chain reaction / risk / Single-nucleotide polymorphism / Software / Tumors