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: Nolt-Helms, Cynthia
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: 23 Displayed | Download in RIS Format

Other center views: All 25 publications 23 publications in selected types All 23 journal articles
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Journal Article Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, Herbstman J, Holland N, LaSalle JM, Schmidt R, Yousefi P, Perera F, Joubert BR, Wiemels J, Taylor M, Yang IV, Chen R, Hew KM, Freeland DM, Miller R, Murphy SK. Small-magnitude effect sizes in epigenetic end points are important in children's environmental health studies: the Children's Environmental Health and Disease Prevention Research Center's Epigenetics Working Group. Environmental Health Perspectives 2017;125(4):511-526. R836159 (2018)
R835436 (2017)
R835442 (2017)
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  • 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)
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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 Felix JF, Joubert BR, Baccarelli AA, Sharp GC, Almqvist C, Annesi-Maesano I, Arshad H, Baiz N, Bakermans-Kranenburg MJ, Bakulski KM, Binder EB, Bouchard L, Breton CV, Brunekreef B, Brunst KJ, Burchard EG, Bustamante M, Chatzi L, Cheng Munthe-Kaas M, Corpeleijn E, Czamara D, Dabelea D, Davey Smith G, De Boever P, Duijts L, Dwyer T, Eng C, Eskenazi B, Everson TM, Falahi F, Fallin MD, Farchi S, Fernandez MF, Gao L, Gaunt TR, Ghantous A, Gillman MW, Gonseth S, Grote V, Gruzieva O, Haberg SE, Herceg Z, Hivert M-F, Holland N, Holloway JW, Hoyo C, Hu D, Huang R-C, Huen K, Jarvelin M-R, Jima DD, Just AC, Karagas MR, Karlsson R, Karmaus W, Kechris KJ, Kere J, Kogevinas M, Koletzko B, Koppelman GH, Kupers LK, Ladd-Acosta C, Lahti J, Lambrechts N, Langie SAS, Lie RT, Liu AH, Magnus MC, Magnus P, Maguire RL, Marsit CJ, McArdle W, Melen E, Melton P, Murphy SK, Nawrot TS, Nistico L, Nohr EA, Nordlund B, Nystad W, Oh SS, Oken E, Page CM, Perron P, Pershagen G, Pizzi C, Plusquin M, Raikkonen K, Reese SE, Reischl E, Richiardi L, Ring S, Roy RP, Rzehak P, Schoeters G, Schwartz DA, Sebert S, Snieder H, Sorensen TIA, Starling AP, Sunyer J, Taylor JA, Tiemeier H, Ullemar V, Vafeiadi M, Van Ijzendoorn MH, Vonk JM, Vriens A, Vrijheid M, Wang P, Wiemels JL, Wilcox AJ, Wright RJ, Xu C-J, Xu Z, Yang IV, Yousefi P, Zhang H, Zhang W, Zhao S, Agha G, Relton CL, Jaddoe VWV, London SJ. Cohort profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. International Journal of Epidemiology 2018;47(1):22-23u. R836159 (2018)
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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)
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  • Journal Article Gonseth S, de Smith AJ, Roy R, Zhou M, Lee S-T, 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)
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  • Journal Article Kaur M, de Smith AJ, Selvin S, Zhang L, Cunningham M, Kang MW, Hansen HM, Cooper RM, McKean-Cowdin R, Wiemels JL, Metayer C. Tobacco smoke and Ras mutations among Latino and non-Latino children with acute lymphoblastic leukemia. Archives of Medical Research 2016;47(8):677-683. R836159 (2018)
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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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  • 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 Miller MD, Valenti M, Schettler T, Tencza B. A story of health: filling a gap in environmental health literacy for health professionals. San Francisco Medicine, Journal of San Francisco Medical Society 2016;89(10):20-24 (Reprinted and edited with permission from Environmental Health Perspective). R836159 (2018)
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  • Journal Article Milne E, Greenop KR, Petridou E, Bailey HD, Orsi L, Kang AY, Baka M, Bonaventure A, Kourti M, Metayer C, Clavel J. Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: a pooled analysis from the Childhood Leukemia International Consortium. Cancer Causes & Control 2018;29(6):539-550. R836159 (2018)
    R834511 (Final)
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  • Journal Article Orsi L, Magnani C, Petridou ET, Dockerty JD, Metayer C, Milne E, Bailey HD, Dessypris N, Kang AY, Wesseling C, Infante-Rivard C, Wunsch-Filho V, Mora AM, Spector LG, Clavel J. Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta-analyses from the Childhood Leukemia International Consortium. Cancer Medicine 2018;7(6):2665-2681. R836159 (2018)
    R834511 (Final)
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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 (19 pp.). R836159 (2017)
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  • Journal Article Petridou ET, Georgakis MK, Erdmann F, Ma X, Heck JE, Auvinen A, Mueller BA, Spector LG, Roman E, Metayer C, Magnani C, Pombo-de-Oliveira MS, Ezzat S, Scheurer ME, Mora AM, Dockerty JD, Hansen J, Kang AY, Wang R, Doody DR, Kane E, Rashed WM, Dessypris N, Schüz J, Infante-Rivard C, Skalkidou A. Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium. European Journal of Epidemiology 2018;33(10):965-976. R836159 (2018)
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  • Journal Article Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM, Bohlin J, XuZ, Huang RC, Reese SE, Xu CJ, Baiz N, Hoyo C, Agha G, Roy R, Holloway JW, Ghantous A, Merid SK, Bakulski KM, Kupers LK, Zhang H, Richmond RC, Page CM, Duijts L, Lie RT, Melton PE, Vonk JM, Nohr EA, Williams-DeVane C, Huen K, Rifas-Shiman SL, Ruiz-Arenas C, Gonseth S, Rezwan FI, Herceg Z, Ekstrom S, Croen L, Falahi F, Perron P, Karagas MR, Quraishi BM, Suderman M, Magnus MC, Jaddoe VWV, Taylor JA, Anderson D, Zhao S, Smit HA, Josey MJ, Bradman A, Baccarelli AA, Bustamante M, Haberg SE, Pershagen G, Hertz-Picciotto I, Newschaffer C, Corpeleijn E, Bouchard L, Lawlor DA, Maguire RL, Barcellos LF, Smith GD, Eskenazi B, Karmaus W, Marsit CJ, Hivert M-F. Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium. Human Molecular Genetics 2017;26(20):4067-4085. R836159 (2018)
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  • Journal Article Wallace AD, Francis SS, Shao X, de Smith AJ, Walsh KM, Mckean-Cowdin R, Ma X, Dahl G, Barcellos LF, Wiemels JL, Metayer C. A germ-line deletion of APOBEC3B does not contribute to subtype-specific childhood acute lymphoblastic leukemia etiology. Haematologica 2018;103(1):e29-e31. R836159 (2018)
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  • Journal Article Wallace AD, Francis SS, Ma X, McKean-Cowdin R, Selvin S, Whitehead TP, Barcellos LF, Kang AY, Morimoto L, Moore TB, Wiemels JL, Metayer C. Allergies and childhood acute lymphoblastic leukemia: a case-control study and meta-analysis. Cancer Epidemiology, Biomarkers and Prevention 2018;27(10):1142-1150. R836159 (2018)
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  • Journal Article Walsh KM, Whitehead TP, de Smith AJ, Smirnov IV, Park M, Endicott AA, Francis SS, Codd V, ENGAGE Consortium Telomere Group, Samani NJ, Metayer C, Wiemels JL. Common genetic variants associated with telomere length confer risk for neuroblastoma and other childhood cancers. Carcinogenesis 2016;37(6):576-582. R836159 (2018)
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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)
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  • Journal Article Wang R, Metayer C, Morimoto L, Wiemels JL, Yang J, DeWan AT, Kang A, Ma X. Parental age and risk of pediatric cancer in the offspring: a population-based record-linkage study in California. American Journal of Epidemiology 2017;186(7):843-856. R836159 (2018)
    R834511 (Final)
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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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  • Journal Article Wiemels JL, Walsh KM, de Smith AJ, Metayer C, Gonseth S, Hansen HM, Francis SS, Ojha J, Smirnov I, Barcellos L, Xiao X, Morimoto L, McKean-Cowdin R, Wang R, Yu H, Hoh J, DeWan AT, Ma X. GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21. Nature Communications 2018;9(1):286 (8 pp.). R836159 (2018)
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  • Progress and Final Reports:

  • 2016 Progress Report
  • 2017 Progress Report
  • 2018 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