||4R01CA239701-02 Interpret this number
||University Of Minnesota
||Admixture Analysis of Acute Lymphoblastic Leukemia in African American Children: the Admiral Study
Modified Project Summary/Abstract Section
Children with substantial African ancestry have long been known to have half or less the rate of B-cell acute
lymphoblastic leukemia (B-ALL) than do children with other continental ancestries. This is true both in
international comparisons of rates of ALL in African nations to those elsewhere, and in comparing rate of B-ALL
in African-American (AA) children to that in European-American (EA) children in the United States. The inverse
association of African ancestry with incidence of B-ALL is independent of established perinatal risk factors for
the disease. Moreover, AA children have lower incidence despite having greater exposure to many putatively
causal environmental risk factors for B-ALL than do EA children. Common genetic variants established by
genomewide association studies incompletely explain the deficit of B-ALL in AA children, suggesting
undiscovered contributing genetic factors may be detected by admixture mapping. We have assembled existing
DNA samples and data for 930 B-ALL patients with AA ancestry and will additionally accrue ~590 over the life
of the project. We will conduct admixture mapping in the assembled group of patients to detect new genetic loci
and new variants at established loci associated with occurrence of B-ALL. In addition, we will examine admixture
in association with clinical characteristics at diagnosis and survival. Candidate genes/variants will be functionally
evaluated through both in silico and in vitro techniques. The proposed research will potentially answer a long-
standing mystery by revealing critical genes or loci that explain the comparative deficit of B-ALL in AA compared
to EA children. In addition, we may uncover genes or variants associated with the worse characteristics at
presentation in AA patients as well as with worse survival, which will indicate avenues for improving outcome
among AA children.
Genetic ancestry, differential gene expression, and survival in pediatric B-cell acute lymphoblastic leukemia.
, Mills L.J.
, Raduski A.R.
, Marcotte E.L.
, Grinde K.E.
, Spector L.G.
, Williams L.A.
Cancer medicine, 2023 Feb; 12(4), p. 4761-4772.