Risk of brain tumors in children and susceptibility to organophosphorus insecticides: The potential role of paraoxonase (PON1)

Susan Searles Nielsen, Beth A. Mueller, Anneclaire J. De Roos, Hannah Malia A. Viernes, Federico M. Farin, Harvey Checkoway

Research output: Contribution to journalArticle

55 Scopus citations

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 PON1C-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.

Original languageEnglish
Pages (from-to)909-913
Number of pages5
JournalEnvironmental Health Perspectives
Volume113
Issue number7
DOIs
StatePublished - Jul 1 2005

Keywords

  • Brain tumor
  • Children
  • Chlorpyrifos
  • Diazinon
  • Dried blood spots
  • Guthrie cards
  • PON1
  • Paraoxonase
  • Pesticides
  • Xenobiotic metabolism

Fingerprint Dive into the research topics of 'Risk of brain tumors in children and susceptibility to organophosphorus insecticides: The potential role of paraoxonase (PON1)'. Together they form a unique fingerprint.

  • Cite this