Center for Integrative Research on Childhood Leukemia and the Environment

EPA Grant Number: R836159
Center: Center for Integrative Research on Childhood Leukemia and the Environment - 2015
Center Director: Metayer, Catherine
Title: Center for Integrative Research on Childhood Leukemia and the Environment
Investigators: Metayer, Catherine
Institution: University of California - Berkeley
EPA Project Officer: Louie, Nica
Project Period: September 1, 2015 through August 31, 2019
Project Amount: $2,599,999
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text |  Recipients Lists
Research Category: Health , Children's Health

Objective:

The goal of the Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) is to identify the causes of childhood acute lymphoblastic leukemia (ALL) and to support prevention efforts by educating health practitioners, families, and public health organizations on risk factors for leukemia. 

Approach:

CIRCLE will integrate population-based and basic research by using archived maternal pregnancy blood specimens and neonatal blood spots from the California Department of Public Health, and will leverage resources from two ongoing studies - the California Childhood Leukemia Study and the California Mother-Child Birth Cohort. Integrated statistical analyses of the Projects will assess the interplay between in utero chemical exposures, immune status, genetics, and epigenetics in ALL etiology. Project 1 will evaluate the impact of in utero chemical exposures on the risk of childhood ALL, taking into account the role of maternal and neonatal immune status, as measured by immunomodulatory cytokines in maternal pregnancy sera and neonatal blood spots. Project 2 will characterize the totality of endogenous and exogenous chemical exposures in maternal and neonatal biospecimens to identify novel in utero risk factors for childhood ALL. New methods for profiling small molecules and protein adducts will be applied, and targeted analyses will be performed for small molecules previously found to be associated with ALL. Project 3 will determine the perturbation of DNA methylation by chemical, immune, and dietary factors, incorporating constitutive genetics, and will evaluate the role of these factors in integrated risk analyses of childhood ALL. Core C will support Projects 1, 2, 3 to elucidate causal mechanisms in a mouse model with a propensity to develop a mouse-analog of childhood ALL. Core B, the Community Outreac and Translation Core, will contribute to environmental health literacy in various audiences, including Latinos, and provide a scientific basis for developing prevention programs for ALL in children.

Rationale:

During the last half century, the incidence of childhood ALL has steadily increased in children, with the highest rates reported in Latinos. This rapid increase strongly supports the role of environmental exposures in the etiology of childhood ALL, either alone or in combination with genetic and epigenetic factors. Existing biological and epidemiological studies suggest that childhood ALL is often initiated in utero and fetal exposure to carcinogenic chemicals may play a role in the etiology of the disease. Given these findings and novel laboratory methods developed during CIRCLE’s first cycle, the overarching theme for the next cycle is to identify additional in utero chemical risk factors for childhood ALL in an ethnically diverse population, and to understand how chemicals increase risk via immunological, genetic and epigenetic mechanisms. 


Journal Articles: 10 Displayed | Download in RIS Format

Other center views: All 12 publications 10 publications in selected types All 10 journal articles
Type Citation Sub Project Document Sources
Journal Article de Smith AJ, Kaur M, Gonseth S, Endicott A, Selvin S, Zhang L, Roy R, Shao X, Hansen HM, Kang AY, Walsh KM, Dahl GV, McKean-Cowdin R, Metayer C, Wiemels JL. Correlates of prenatal and early-life tobacco smoke exposure and frequency of common gene deletions in childhood acute lymphoblastic leukemia. Cancer Research 2017;77(7):1674-1683. R836159 (2017)
R836159C003 (2017)
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  • Journal Article Edmands WMB, Petrick LM, Barupal DK, Scalbert A, Wilson MJ, Wickliffe JK, Rappaport SM. compMS2Miner:an automatable metabolite identification, visualization, and data-sharing R package for high-resolution LC-MS data sets. Analytical Chemistry 2017;89(7):3919-3928. R836159 (2017)
    R836159C002 (2017)
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  • Journal Article Giddings BM, Whitehead TP, Metayer C, Miller MD. Childhood leukemia incidence in California: high and rising in the Hispanic population. Cancer 2016;122(18):2867-2875. R836159 (2017)
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  • Journal Article Gonseth S, Roy R, Houseman EA, de Smith AJ, Zhou M, Lee ST, Nussle S, Singer AW, Wrensch MR, Metayer C, Wiemels JL. Periconceptional folate consumption is associated with neonatal DNA methylation modifications in neural crest regulatory and cancer development genes. Epigenetics 2015;10(12):1166-1176. R836159 (2017)
    R836159C003 (2016)
    R834511 (2014)
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  • Journal Article Gonseth S, de Smith AJ, Roy R, Zhou M, Lee ST, Shao X, Ohja J, Wrensch MR, Walsh KM, Metayer C, Wiemels JL. Genetic contribution to variation in DNA methylation at maternal smoking-sensitive loci in exposed neonates. Epigenetics 2016;11(9):664-673. R836159 (2017)
    R836159C003 (2017)
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  • Journal Article Metayer C, Dahl G, Wiemels J, Miller M. Childhood leukemia: a preventable disease. Pediatrics 2016;138 (Suppl 1):S45-S55. R836159 (2017)
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  • Abstract: Pediatrics-Abstract
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  • Journal Article Miller MD, Valenti M, Schettler T, Tencza B. A multimedia e-book — a story of health: filling a gap in environmental health literacy for health professionals. Environmental Health Perspectives 2016;124(8):A133-A136. R836159 (2017)
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  • Journal Article Petrick L, Edmands W, Schiffman C, Grigoryan H, Perttula K, Yano Y, Dudoit S, Whitehead T, Metayer C, Rappaport S. An untargeted metabolomics method for archived newborn dried blood spots in epidemiologic studies. Metabolomics 2017;13(3):27. R836159 (2017)
    R836159C002 (2017)
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  • Abstract: Springer-Abstract
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  • Journal Article Wang R, Wiemels JL, Metayer C, Morimoto L, Francis SS, Kadan-Lottick N, DeWan AT, Zhang Y, Ma X. Cesarean section and risk of childhood acute lymphoblastic leukemia in a population-based, record-linkage study in California. American Journal of Epidemiology 2017;185(2):96-105. R836159 (2017)
    R836159C001 (2017)
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  • Journal Article Whitehead TP, Metayer C, Wiemels JL, Singer AW, Miller MD. Childhood leukemia and primary prevention. Current Problems in Pediatric and Adolescent Health Care 2016;46(10):317-352. R836159 (2017)
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  • Progress and Final Reports:

    2016 Progress Report
    2017 Progress Report

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R836159C001 In Utero Chemical Exposures, Immune Status, and Childhood Leukemia
    R836159C002 Identifying In Utero Exposures that are Risk Factors for Childhood Leukemia
    R836159C003 Prenatal Exposures, Constitutive Genetics, DNA Methylation & Childhood Leukemia