ABSTRACT
Leukemia is the most common pediatric cancer affecting more than 40,000 children worldwide each year. During
the last decades, childhood leukemia incidence has increased in the US by ~35% overall, with an even larger
rise among LatinX. Similar trends are also observed in several Latin American countries. This rapid increase
points to the critical role of environmental factors in the development childhood leukemia, possibly in combination
with genetic factors. Despite improved prognosis of childhood leukemia overall, there are major differences by
subtype, region, racial/ethnic group, and socio-economic status, and leukemia survivors remain at risk for serious
lifelong complications. Altogether, these observations highlight the need to support more research and
prevention to reduce leukemia burden and disparity. The overall objective of this U24 competing renewal is to
expand the support of existing population studies (here case-control design) to accelerate childhood leukemia
environmental research and prevention, with a focus on LatinX populations. In the first R24 cycle (2017-22), we
maintained and enhanced the resources and data sharing of two NIEHS-funded studies with large numbers of
LatinX children in California, United States and Guatemala. To further address childhood leukemia disparity in
LatinX, while increasing diversity of the research team, we now propose to (i) include additional childhood
leukemia studies with low-resources in Mexico and Costa Rica, (ii) coordinate research translation/prevention
among participating countries, and (iii) collaborate with LatinX researchers and health workers in California and
Latin America. The four participating studies have enrolled 8,480 childhood leukemia cases and 4,462 controls,
and have collected a wealth of environmental/genetic data and biospecimens providing the most comprehensive
resources in LatinX populations worldwide. Individually or as part of the Childhood Cancer and Leukemia
Consortium (CLIC), these studies have produced seminal findings, documenting the prenatal origin of childhood
leukemia and identifying many factors that contribute to the increased or decreased risks of the disease including
chemical exposures, diet/vitamins, breastfeeding, immune response, birthweight and genetic factors. The
maintenance of these resources and the enhancement of data sharing procedures are needed to efficiently
expand ongoing etiologic and tumor-biology studies of childhood leukemia, especially myeloid subtypes which
are more common in LatinX, and uncover sources of disparity in leukemia risk and outcomes. To achieve our
goals, we plan to (1) use an interoperable management system REDCap to provide unifying support for
management, harmonization, storage and sharing of study resources; (2) enrich case-control studies by
conducting linkages to population-level databases on exposures to potential carcinogenic agents/mixtures and
social/built environments; (3) facilitate broader data use nationally and internationally with the CLIC Consortium,
and (4) expand community engagement with the public, lay health workers, and health professionals in the US
and Latin American countries to increase awareness about preventable risk factors of childhood leukemia.