Cohort-Based Association Study Association of Genetic Variations of ABCC with the Non-Response and Relapse of Pediatric Patients with Central Nervous System Tumors

Objectives: The variability in outcomes among individuals is caused by multiple factors, including genetic variations in drug transporter genes known as ABCs. This study investigates the clinical impact of single nucleotide variants (SNV) in the ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 genes on the clinical response and relapse of pediatric patients with central nervous system tumors. Methods: In a study involving 111 cancer patients, genotyping of ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 was conducted using real-time PCR with TaqMan probes. Treatment response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Univariate and multivariate analyses using the Cox proportional hazards (adjusted) model. Multivariate analysis adjusted for sex and age showed a significant association between ABCC1 r.5540G>C; rs12921623 in the gene and non-response to treatment in the codominant model HR=2.095 (95% CI 1.202-3.650) p= 0.009 and in the dominant model HR= 2.025 (95% CI 1.199 -3.421), p=0. 008 and an increased risk of relapse in the codominant model HR= 9.09 (95% CI 1.04-78.85) p=0.04 and the dominant model HR= 3.912 (95% CI 1.139-13.436) p= 0.03. Furthermore, a significant association was found between ABCC2 c. 3972C>T; rs3740066 and relapse in the recessive model HR=3.5 (95% CI 1.02-12.17) p= 0.04. Conclusions: Our findings indicate that ABCC1 r.5540 G>C SNV and in the ABCC2 c. 3972C>T SNV are significant predictors of non-response and relapse in this group of pediatric patients with central nervous system tumors.