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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES018172-04
Application #
8513512
Study Section
Special Emphasis Panel (ZES1-LKB-G (P1))
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$149,047
Indirect Cost
$91,320
Name
University of California Berkeley
Department
Type
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
de Smith, Adam J; Kaur, Maneet; Gonseth, Semira et al. (2017) Correlates of Prenatal and Early-Life Tobacco Smoke Exposure and Frequency of Common Gene Deletions in Childhood Acute Lymphoblastic Leukemia. Cancer Res 77:1674-1683
Wang, Rong; Wiemels, Joseph L; Metayer, Catherine et al. (2017) Cesarean Section and Risk of Childhood Acute Lymphoblastic Leukemia in a Population-Based, Record-Linkage Study in California. Am J Epidemiol 185:96-105
Gunier, Robert B; Kang, Alice; Hammond, S Katharine et al. (2017) A task-based assessment of parental occupational exposure to pesticides and childhood acute lymphoblastic leukemia. Environ Res 156:57-62
Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire et al. (2016) Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC). Lancet Haematol 3:e176-85
de Smith, Adam J; Ojha, Juhi; Francis, Stephen S et al. (2016) Clonal and microclonal mutational heterogeneity in high hyperdiploid acute lymphoblastic leukemia. Oncotarget 7:72733-72745
Metayer, Catherine; Petridou, Eleni; Aranguré, Juan Manuel Mejía et al. (2016) Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium. Am J Epidemiol 184:261-73
Lee, Seung-Tae; Wiemels, Joseph L (2016) Genome-wide CpG island methylation and intergenic demethylation propensities vary among different tumor sites. Nucleic Acids Res 44:1105-17
Morimoto, Libby M; McCauley, Kathryn; Ma, Xiaomei et al. (2016) Birth weight, fetal growth, and risk of pediatric rhabdomyosarcoma: an updated record linkage study in California. Ann Epidemiol 26:141-145
Metayer, Catherine; Dahl, Gary; Wiemels, Joe et al. (2016) Childhood Leukemia: A Preventable Disease. Pediatrics 138:S45-S55
Giddings, Brenda M; Whitehead, Todd P; Metayer, Catherine et al. (2016) Childhood leukemia incidence in California: High and rising in the Hispanic population. Cancer 122:2867-75

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