Novel Genetic Risk Factor Identified for L-Asparaginase-Induced Pancreatitis in Pediatric Patients With Cancer

GWAS in 1086 pediatric ALL patients, rs149210846 variant associated (OR=8.9, p=1.8×10⁻⁸) with L-asparaginase-induced severe grade 3-4 pancreatitis, independently replicated, risk multiplied by ancestry (Admixed-American, Asian)

A GWAS study in 1086 pediatric patients treated with L-asparaginase for acute lymphoblastic leukemia identifies and replicates the rs149210846 variant as a genetic risk factor for severe (grade 3-4) L-asparaginase-induced pancreatitis. Carriers show 5.9- to 7.7-fold increased risk depending on pancreatitis grade. Risk is significantly higher in patients of Admixed-American (OR=8.8) and Asian (OR=10.0) genetic ancestry, highlighting the importance of genetic diversity in chemotherapy toxicity pharmacogenomics.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Severe L-asparaginase-induced pancreatitis is a potentially fatal complication and common reason for treatment discontinuation in pediatric ALL. The identification of rs149210846 with OR >8 is a clinically significant advance: it opens the path to preemptive genotyping to adapt monitoring and anticipate L-asparaginase discontinuation or substitution in carriers. The excess risk in Admixed-American and Asian ancestries should be integrated into targeted screening strategies.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 10/10