Genomics of childhood leukemia: Analysis of diverse, worldwide populations
University of Minnesota
Project Term: March 1, 2022 - February 29, 2024
Common genetic variation explains a large share of childhood leukemia in children of European ancestry and may explain the differing incidence in children of other ancestries. The Childhood Cancer and Leukemia International Consortium seeks to better understand the genomic architecture of childhood leukemia risk using its collective genomic datasets comprising >20,000 diverse children with leukemia. The results will inform risk prediction for and possibly prevention of childhood leukemia.
Childhood leukemia shows distinct patterns of incidence by ancestry. In the United States acute lymphoblastic leukemia (ALL) risk is highest in Latinos, followed by European and Asian/Pacific Islander children, while African-American children have by far the lowest rates. There is strong reason to believe these patterns may be based at least partially on genetics. For instance, incidence of childhood leukemia among diaspora populations in the United States largely recapitulates patterns of international incidence. Genomewide association studies (GWAS) have successfully identified robust associations with genetic variants for ALL in children of European ancestry. However, while initial genetic investigations of ALL of children in other ancestries suggest genetic variation may explain differing patterns of incidence, there has been no robust, systematic attempt to study the matter to date. GWAS of childhood acute myeloid leukemia (AML) have yet to be published. The Childhood Cancer and Leukemia International Consortium (CLIC) is ideally suited to understanding the genomic architecture of childhood leukemia risk in children of many ancestries. CLIC’s collective genomic datasets comprise >12,000 children with ALL and AML from five continents, making it both the largest and most diverse such datasets worldwide. When combined with publicly available genotypes from another ~10,800 leukemias, the combined resource will exceed 20,000 children with leukemia and >100,000 controls. CLIC investigators will aggregate, clean, and harmonize existing childhood cancer germline genotype data to enable large-scale analysis. Following this, CLIC investigators will conduct initial GWAS for ALL and AML, separately, both within and across ancestries. GWAS summary statistics will then be made available for other researchers’ use. At the conclusion of this study, CLIC will have articulated a far more comprehensive genetic epidemiology of ALL and AML than exists today in populations that represent most of the children on Earth. The results will inform risk prediction for and possibly prevention of childhood leukemia.