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Exposure Assessment for Childhood LeukemiaEPA Grant Number: R834511C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834511
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE)
Center Director: Buffler, Patricia
Title: Exposure Assessment for Childhood Leukemia
Investigators: Buffler, Patricia
Institution: University of California - Berkeley , Stanford University , University of California - San Francisco
EPA Project Officer: Louie, Nica
Project Period: September 25, 2009 through September 24, 2015
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Health
Previous case-control studies of childhood leukemi mostly relied on self-reported exposure which lack specificity and may suffer from recall bias. The proposed study builds upon a large case-control study, the Northern California Childhood Leukemia Study (NCCLS) to improve chemical exposure assessment, using available home dust samples and a variety of biospecimens. Preliminary NCCLS findings suggest that house dust can provide useful quantitative surrogates for in-home exposures to toxic contaminants. In order to assess whether persistent contaminants such as nicotine (a surrogate for ETS), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) accumulate in house dust over several years, the proposed study will obtain an additional household-dust sample from each of 150 homes in the NCCLS population for which we have existing dust samples. To further validate the use of house dust as a measure of children's exposures to toxic substances, we will measure nicotine, PCBs, and PBDEs in serum samples obtained from about 250 childhood leukemia cases at diagnosis and then determine correlations between analyte levels in serum and house dust. In addition, the NCCLS obtained archived newborn dried blood spot (DBS) collected at birth. Since blood and DBS contain adducts of potential carcinogens with hemoglobin (Hb) and human serum albumin (HSA), they offer opportunities for quantifying children's exposures and internal doses during one or two months prior to collection.
Using methods developed in our laboratory, we will detect and profile cysteinyl adducts of HSA in pre-treatment diagnostic blood from children with leukemia and in newborn DBS from a subset of 200 children (100 cases and 100 controls; these subjects will be among those investigated for DNA methylation patterns in Project 3). By comparing DBS-adduct profiles between childhood leukemia case and control children, we will detect particular adducts that are associated with disease status. Then, after chemically identifying these adducts and their likely precursors, we will pinpoint eariy life exposures that increase the risk of childhood leukemia, and possible changes in levels of important adducts between birth and diagnosis.
Supplemental Keywords:House dust, biomarkers, dried blood spot, exposure assessment, risk assessment, sensitive population, carcinogens, population, infants, children, genetic pre-disposition, genetic susceptibility, Hispanics, PAH, PCB, PBDE, nicotine, pesticides, public policy, decision making, community-based, public health, environmental epidemiology, genetics, toxicology, biostatistics, epigenetic, modeling, gene-environment interaction, measurement methods, California, international,
Main Center Abstract and Reports:R834511 Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE)
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834511C001 Childhood Leukemia International Consortium Studies
R834511C002 Exposure Assessment for Childhood Leukemia
R834511C003 Prenatal Exposures, DNA Methylation & Childhood Leukemia