ABCC Gene Variants and Their Effects on Non-Response and Relapse in Pediatric Patients with Central Nervous System Tumors: A Cohort Study

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 effect of single-nucleotide variants (SNVs) in the <i>ABCC1</i>/<i>MRP1</i>, <i>ABCC2</i>/<i>MRP2</i>, and <i>ABCC4</i>/<i>MRP4</i> genes on the clinical response and relapse of pediatric patients with central nervous system tumors. In a cohort-based association study involving 111 cancer patients, genotyping of <i>ABCC1</i>/<i>MRP1</i>, <i>ABCC2</i>/<i>MRP2</i>, and <i>ABCC4</i>/<i>MRP4</i> was conducted using real-time PCR with TaqMan probes. Treatment response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. Univariate and multivariate analyses were conducted using the Cox proportional hazards (adjusted) model. Multivariate analysis adjusted for sex and age showed a significant association between <i>ABCC1</i> r.5540out G>C; rs12921623 in the gene and non-response to treatment in the codominant model [HR] 2.095, 95% CI 1.202-3.650, <i>p</i> = 0.009, and in the dominant model [HR] 2.025, 95% CI 1.199-3.421, <i>p</i> = 0.008, and an increased risk of relapse in the codominant model [HR] 9.09, 95% CI 1.04-78.85, <i>p</i> = 0.04, and in the dominant model [HR] 3.912, 95% CI 1.139-13.436, <i>p</i> = 0.03. Furthermore, a significant association was found between <i>ABCC2</i> c. 3972 C>T; rs3740066 and relapse in the recessive model [HR] 3.5, 95% CI 1.02-12.17, <i>p</i> = 0.04. Our findings indicate that <i>ABCC1</i> r.5540 G>C SNV and <i>ABCC2</i> c. 3972 C>T SNV are significant predictors of non-response and relapse in this group of pediatric patients with central nervous system tumors.