Previous case-control studies of childhood leukemia 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 early life exposures that increase the risk of childhood leukemia, and possible changes in levels of important adducts between birth and diagnosis.
The purpose of this project is to assess exposures to persistent contaminants present in homes that may cause leukemia, based upon analysis of house dust, blood collected at the time of the diagnosis of leukemia cases, and archived newborn dried blood spots collected at birth.
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