Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia

Yang W, Karol SE, Hoshitsuki K, Lee S, Larsen EC, Winick N, Carroll WL, Loh ML, Raetz EA, Hunger SP, Winter SS, Dunsmore KP, Devidas M, Relling MV, Yang JJ. Association of Inherited Genetic Factors With Drug-Induced Hepatic Damage Among Children With Acute Lymphoblastic Leukemia. JAMA Netw Open. 2022 Dec 1;5(12):e2248803. doi: 10.1001/jamanetworkopen.2022.48803. PubMed PMID: 36580335; PubMed Central PMCID: PMC9857512.

This retrospective analysis of a multiethnic genome-wide association study was conducted between January 1, 2019, and April 15, 2022, including patients treated as part of Children’s Oncology Group (COG) trials with centers in the United States, Canada, and Australia, which accrued data from December 29, 2003, to January 21, 2011 (AALL0232), and from January 22, 2007, to July 24, 2014 (AALL0434). Germline genotypes were interrogated using genome-wide arrays and imputed using a National Institutes of Health TOPMed Imputation server. Mixed-effects logistic regressions were used to account for multiple episodes for an individual patient. Genotype × treatment phase interaction was tested to uncover phase-specific genetic risk factors.