Grant Number:	1R03CA106011-01 Interpret this number
Primary Investigator:	Mueller, Beth
Organization:	Fred Hutchinson Can Res Ctr
Project Title:	Exploring Gene-Environment Factors in Child Brain Tumors
Fiscal Year:	2003

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.




A genome-wide association study on medulloblastoma.
Authors: Dahlin A.M. , Wibom C. , Andersson U. , Bybjerg-Grauholm J. , Deltour I. , Hougaard D.M. , Scheurer M.E. , Lau C.C. , McKean-Cowdin R. , Kennedy R.J. , et al. .
Source: Journal Of Neuro-oncology, 2020-02-13 00:00:00.0; , .
EPub date: 2020-02-13 00:00:00.0.
PMID: 32056145
Related Citations

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.
PMID: 26316358
Related Citations

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.
PMID: 25628003
Related Citations

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 00:00:00.0; 84(1), p. 81-8.
PMID: 25398229
Related Citations

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
Related Citations

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
Related Citations

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.
PMID: 23647384
Related Citations

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.
PMID: 24260161
Related Citations

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.
PMID: 22335454
Related Citations

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
Related Citations

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.
PMID: 21914837
Related Citations

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 00:00:00.0; 5(9), p. 7555-64.
PMID: 21842844
Related Citations

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.
PMID: 21624820
Related Citations

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; 6(3), p. e18376.
PMID: 21464892
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations