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

## TL;DR

This study finds that specific genetic variants in ABCC1 and ABCC2 genes are linked to poor treatment response and higher relapse risk in children with brain tumors.

## Contribution

The study identifies novel associations between ABCC1 and ABCC2 gene variants and clinical outcomes in pediatric CNS tumor patients.

## Key findings

- ABCC1 r.5540 G>C variant is significantly associated with non-response and relapse in pediatric CNS tumor patients.
- ABCC2 c.3972 C>T variant is significantly linked to relapse in a recessive model.
- Multivariate analysis confirms the predictive value of these SNVs after adjusting for age and sex.

## Abstract

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 ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 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 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. 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 ABCC1 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, 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 in the dominant model [HR] 3.912, 95% CI 1.139–13.436, p = 0.03. Furthermore, a significant association was found between ABCC2 c. 3972 C>T; rs3740066 and relapse in the recessive model [HR] 3.5, 95% CI 1.02–12.17, p = 0.04. Our findings indicate that ABCC1 r.5540 G>C SNV and ABCC2 c. 3972 C>T SNV are significant predictors of non-response and relapse in this group of pediatric patients with central nervous system tumors.