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Grant Details

Grant Number: 5R03CA106011-02 Interpret this number
Primary Investigator: Mueller, Beth
Organization: Fred Hutchinson Cancer Research Center
Project Title: Exploring Gene-Environment Factors in Child Brain Tumors
Fiscal Year: 2004
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Abstract

DESCRIPTION (provided by applicant): The causes of childhood brain tumors (CBT) are largely unknown. Environmental exposures are thought to play a role due to the vulnerability of fetal and early childhood brain to environmental toxins. This project would improve our limited understanding of the relationships of environmental and genetic factors in CBT occurrence by providing necessary preliminary data about the frequency of selected polymorphisms in CBT cases and controls, and demonstrating the feasibility of measuring polymorphisms in dried blood spots (DBS) from newborn screening archives for population-based epidemiologic studies of CBT, thus positioning us for larger CBT studies examining genes and environment. We have an opportunity to gain this information efficiently and economically, as specimens and exposure data already have been obtained. We propose to measure polymorphisms for genes which code for enzymes that metabolize chemicals potentially related to CBT occurrence, in DBS collected from 66 CBT cases and 237 controls. We will compare polymorphisms for the following genes: 1) Cytochrome P-450 (CYP) 2E1 and CYP 2D6, coding Phase I enzymes that activate nitrosamines and other chemicals into cancer-causing intermediates; 2) Glutathione S-transferase (GST) (GSTP1, GSTT1, and GSTM1), which code for Phase II enzymes that detoxify organochlorine pesticides, nitrosoureas, CYP-activated nitrosamines, polycyclic aromatic hydrocarbons (PAH); 3) Microsomal epoxide hydrolase, relevant to activation of PAHs into cancer-causing intermediates; 4) Paraoxonase (PON1), potentially important in detoxifying metabolites of the common organophosphate (OP) insecticides chlorpyrifos and diazinon. To the extent possible with these data, we will describe polymorphisms within histologic categories and by age at diagnosis, and examine their relationship with relevant environmental exposures among a subset of subjects with exposure data for the prenatal and early childhood periods.

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Publications

Genetic targeting of protease activated receptor 2 reduces inflammatory astrogliosis and improves recovery of function after spinal cord injury.
Authors: Radulovic M. , Yoon H. , Wu J. , Mustafa K. , Fehlings M.G. , Scarisbrick I.A. .
Source: Neurobiology of disease, 2015 Nov; 83, p. 75-89.
EPub date: 2015-08-24.
PMID: 26316358
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The thrombin receptor is a critical extracellular switch controlling myelination.
Authors: Yoon H. , Radulovic M. , Drucker K.L. , Wu J. , Scarisbrick I.A. .
Source: Glia, 2015 May; 63(5), p. 846-59.
EPub date: 2015-01-27.
PMID: 25628003
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Relapses and disability accumulation in progressive multiple sclerosis.
Authors: Paz Soldán M.M. , Novotna M. , Abou Zeid N. , Kale N. , Tutuncu M. , Crusan D.J. , Atkinson E.J. , Siva A. , Keegan B.M. , Pirko I. , et al. .
Source: Neurology, 2015-01-06; 84(1), p. 81-8.
EPub date: 2014-11-14.
PMID: 25398229
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Polyclonal and monoclonal antibodies in clinic.
Authors: Wootla B. , Denic A. , Rodriguez M. .
Source: Methods in molecular biology (Clifton, N.J.), 2014; 1060, p. 79-110.
PMID: 24037837
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Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration.
Authors: Radulovic M. , Yoon H. , Larson N. , Wu J. , Linbo R. , Burda J.E. , Diamandis E.P. , Blaber S.I. , Blaber M. , Fehlings M.G. , et al. .
Source: Journal of neuropathology and experimental neurology, 2013 Nov; 72(11), p. 1072-89.
PMID: 24128681
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Kallikrein 6 signals through PAR1 and PAR2 to promote neuron injury and exacerbate glutamate neurotoxicity.
Authors: Yoon H. , Radulovic M. , Wu J. , Blaber S.I. , Blaber M. , Fehlings M.G. , Scarisbrick I.A. .
Source: Journal of neurochemistry, 2013 Oct; 127(2), p. 283-98.
EPub date: 2013-05-27.
PMID: 23647384
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Parental smoking and risk of childhood brain tumors by functional polymorphisms in polycyclic aromatic hydrocarbon metabolism genes.
Authors: Barrington-Trimis J.L. , Searles Nielsen S. , Preston-Martin S. , Gauderman W.J. , Holly E.A. , Farin F.M. , Mueller B.A. , McKean-Cowdin R. .
Source: PloS one, 2013; 8(11), p. e79110.
EPub date: 2013-11-18.
PMID: 24260161
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Kallikrein 6 regulates early CNS demyelination in a viral model of multiple sclerosis.
Authors: Scarisbrick I.A. , Yoon H. , Panos M. , Larson N. , Blaber S.I. , Blaber M. , Rodriguez M. .
Source: Brain pathology (Zurich, Switzerland), 2012 Sep; 22(5), p. 709-22.
EPub date: 2012-03-21.
PMID: 22335454
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Naturally occurring antibodies as therapeutics for neurologic disease: can human monoclonal IgMs replace the limited resource IVIG?
Authors: Warrington A.E. , Van Keulen V. , Pease L.R. , Rodriguez M. .
Source: Advances in experimental medicine and biology, 2012; 750, p. 44-55.
PMID: 22903665
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Childhood brain tumors and maternal cured meat consumption in pregnancy: differential effect by glutathione S-transferases.
Authors: Searles Nielsen S. , Mueller B.A. , Preston-Martin S. , Farin F.M. , Holly E.A. , McKean-Cowdin R. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011 Nov; 20(11), p. 2413-9.
EPub date: 2011-09-13.
PMID: 21914837
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Facile assembly of micro- and nanoarrays for sensing with natural cell membranes.
Authors: Wittenberg N.J. , Im H. , Johnson T.W. , Xu X. , Warrington A.E. , Rodriguez M. , Oh S.H. .
Source: ACS nano, 2011-09-27; 5(9), p. 7555-64.
EPub date: 2011-08-17.
PMID: 21842844
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Autoantibodies with enzymatic properties in human autoimmune diseases.
Authors: Wootla B. , Lacroix-Desmazes S. , Warrington A.E. , Bieber A.J. , Kaveri S.V. , Rodriguez M. .
Source: Journal of autoimmunity, 2011 Sep; 37(2), p. 144-50.
EPub date: 2011-05-31.
PMID: 21624820
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Functional role of kallikrein 6 in regulating immune cell survival.
Authors: Scarisbrick I.A. , Epstein B. , Cloud B.A. , Yoon H. , Wu J. , Renner D.N. , Blaber S.I. , Blaber M. , Vandell A.G. , Bryson A.L. .
Source: PloS one, 2011-03-28; 6(3), p. e18376.
EPub date: 2011-03-28.
PMID: 21464892
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Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes.
Authors: Searles Nielsen S. , McKean-Cowdin R. , Farin F.M. , Holly E.A. , Preston-Martin S. , Mueller B.A. .
Source: Environmental health perspectives, 2010 Jan; 118(1), p. 144-9.
PMID: 20056567
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Newborn screening archives as a specimen source for epidemiologic studies: feasibility and potential for bias.
Authors: Searles Nielsen S. , Mueller B.A. , De Roos A.J. , Checkoway H. .
Source: Annals of epidemiology, 2008 Jan; 18(1), p. 58-64.
PMID: 18063239
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Risk of brain tumors in children and susceptibility to organophosphorus insecticides: the potential role of paraoxonase (PON1).
Authors: Searles Nielsen S. , Mueller B.A. , De Roos A.J. , Viernes H.M. , Farin F.M. , Checkoway H. .
Source: Environmental health perspectives, 2005 Jul; 113(7), p. 909-13.
PMID: 16002382
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