Genome-Wide Association Study of Relapse of Childhood Acute Lymphoblastic Leukemia

Using risk-directed therapy for childhood acute lymphoblastic leukemia (ALL), outcome has improved dramatically in the last 40 years. However, a substantial portion of patients experience relapse, many of whom have no known risk factors. Taking a genome-wide approach, we sought to evaluate the relationships between germline SNP genotypes and the risk of relapse in 2,535 children with newly diagnosed ALL after adjusting for genetic ancestry and treatment regimen. We examine prognostic value of selected SNPs in the context of known relapse risk factors (molecular subtypes, minimal residual disease, age and leukocyte count at diagnosis). Associations of relapse-related SNPs with pharmacokinetic and pharmacodynamics of antileukemic drugs offer plausible mechanism by which they are linked to treatment outcome. Finally, we aim to identify SNPs that are related to both genetic ancestry and relapse which are likely to contribute to racial disparities in ALL survival. ]]>
Inclusion/exclusion was based on enrollment on the clinical trials of ALL at St. Jude Children Research Hospital and the Children Oncology Group, informed consent following OPRR guidelines, availability of germline DNA, and data quality in subsequent genotyping experiments.]]>
Children with newly diagnosed ALL treated on St. Jude Children Research Hospital protocols Total Therapy XIIIB or Total XV, or the Children Oncology Group (COG) protocols P9906, P9904, or P9905.]]>