Ethnic Differences in the Association Between SOD2 rs4880 and Hepatotoxicity in Pediatric Acute Lymphoblastic Leukemia: A Report From the REDIAL Consortium.

Treatment-associated hepatotoxicity (TAH) is a common complication of pediatric acute lymphoblastic leukemia (ALL) treatment, but genetic risk factors remain poorly understood. We evaluated the SOD2 rs4880 variant in 544 children with ALL at Texas Children's Hospital. After adjusting for demographic and clinical covariates, the rs4880 C allele was associated with an increased odds of conjugated hyperbilirubinemia and/or Grade 4 transaminitis in Hispanic children (adjusted odds ratio [aOR] = 2.73, 95% confidence interval [CI]: 1.72-4.47; p = 3.5 × 10), but decreased odds in non-Hispanic children (aOR = 0.55, 95% CI: 0.32-0.94, p = 0.03). These findings highlight potential ethnicity-specific differences in genetic contributors to TAH risk and highlight the need for mechanistic studies.