In JAMA Network Open, researchers at the St. Jude Children's Research Hospital, Maine Children's Cancer Program, and elsewhere search for genetic variants linked to hepatotoxic side effects in children being treated for acute lymphoblastic leukemia (ALL). With array-based genotyping profiles for nearly 3,600 participants from two Children's Oncology Group trials, the team searched for germline variants linked to liver damage markers such as grade 3 or higher hyperbilirubinemia, higher-than-usual alanine aminotransferase enzyme levels, and enhanced levels of aspartate aminotransferase. When they focused on 576 variants linked to liver enzyme levels or injury in a prior genome-wide association study involving individuals from the general population, for example, the authors found UGT1A1 and PNPLA3 variants coinciding with hyperbilirubinemia or ALT and AST levels in the pediatric ALL patients going through treatment. The UGT1A1 and PNPLA3 genes also fell into a hepatotoxicity-related polygenic risk score for children on treatment, they report, while a GWAS analyses on the ALL patients highlighted a CPT1A-neighboring variant with ties to increased ALT and AST levels in ALL patients under 10 years old. "These findings suggest that there is an association between genetic factors and interpatient variability in the occurrence of hepatotoxic effects during treatment for ALL," the researchers write.
Study Reveals Genetic Contributors to Treatment-Related Liver Damage in Pediatric Leukemia Patients
Jan 03, 2023