Journal article
Risk of Brain Tumors in Children and Susceptibility to Organophosphorus Insecticides: The Potential Role of Paraoxonase (PON1)
Environmental health perspectives, v 113(7), pp 909-913
18 Mar 2005
PMCID: PMC1257655
PMID: 16002382
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Prior research suggests that childhood brain tumors (CBTs) may be associated with exposure to pesticides. Organophosphorus insecticides (OPs) target the developing nervous system, and until recently, the most common residential insecticides were chlorpyrifos and diazinon, two OPs metabolized in the body through the cytochrome P450/paraoxonase 1 (PON1) pathway. To investigate whether two common
PON1
polymorphisms, C-108T and Q192R, are associated with CBT occurrence, we conducted a population-based study of 66 cases and 236 controls using DNA from neonatal screening archive specimens in Washington State, linked to interview data. The risk of CBT was nonsignificantly increased in relation to the inefficient
PON1
promoter allele [per
PON1
-108T
allele, relative to
PON1
-108CC
: odds ratio (OR) = 1.4; 95% confidence interval (CI), 1.0–2.2;
p
-value for trend = 0.07]. Notably, this association was strongest and statistically significant among children whose mothers reported chemical treatment of the home for pests during pregnancy or childhood (per
PON1
-108T
allele: among exposed, OR = 2.6; 95% CI, 1.2–5.5; among unexposed, OR = 0.9; 95% CI, 0.5–1.6) and for primitive neuroectodermal tumors (per
PON1
-108T
allele: OR = 2.4; 95% CI, 1.1–5.4). The Q192R polymorphism, which alters the structure of PON1 and influences enzyme activity in a substrate-dependent manner, was not associated with CBT risk, nor was the
PON1
C-108T/Q192R
haplotype. These results are consistent with an inverse association between PON1 levels and CBT occurrence, perhaps because of PON1’s ability to detoxify OPs common in children’s environments. Larger studies that measure plasma PON1 levels and incorporate more accurate estimates of pesticide exposure will be required to confirm these observations.
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Details
- Title
- Risk of Brain Tumors in Children and Susceptibility to Organophosphorus Insecticides: The Potential Role of Paraoxonase (PON1)
- Creators
- Susan Searles Nielsen - Fred Hutch Cancer CenterBeth A. Mueller - Fred Hutch Cancer CenterAnneclaire J. De Roos - Fred Hutchinson Cancer Research CenterHannah-Malia A. Viernes - University of WashingtonFederico M. Farin - University of WashingtonHarvey Checkoway - University of Washington
- Publication Details
- Environmental health perspectives, v 113(7), pp 909-913
- Publisher
- National Institue of Environmental Health Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Environmental and Occupational Health
- Web of Science ID
- WOS:000230250800041
- Scopus ID
- 2-s2.0-22144452878
- Other Identifier
- 991020099800804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Environmental Sciences
- Public, Environmental & Occupational Health
- Toxicology