| Risk of Brain Tumors in Children and Susceptibility to Organophosphorus Insecticides: The Potential Role of Paraoxonase (PON1) Susan Searles Nielsen,1,2 Beth A. Mueller,1,2 Anneclaire
J. De Roos,1,2 Hannah-Malia A.Viernes,3
Federico M. Farin,3 and Harvey Checkoway1,2,3 1Public Health Sciences Division, Fred Hutchinson Cancer Research
Center, Seattle, Washington, USA; 2Department of Epidemiology and 3Department
of Environmental and Occupational Health Sciences, School of Public Health
and Community Medicine, University
of Washington, Seattle, Washington, USA 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. Key words: brain tumor, children, chlorpyrifos, diazinon, dried blood spots, Guthrie cards, paraoxonase, pesticides, PON1, xenobiotic metabolism. Environ Health Perspect 113: 909-913 (2005) . doi:10.1289/ehp.7680 available via http://dx.doi.org/ [Online 18 March 2005]
Address correspondence to S. Searles Nielsen, Fred Hutchinson Cancer Research Center, P.O. Box 19024, 1100 Fairview Ave. North, MS M4-C308, Seattle, WA 98109-1024 USA. Telephone: (206) 667-7613. Fax: (206) 667-5948. E-mail: snielsen@fhcrc.org We thank the Washington State Department of Health Newborn Screening Program, M. Glass, and M. Ginder ; and C. Furlong and G. Jarvik, University of Washington, Medical Genetics. This work was supported by grants NIEHS T32ES07262, NIEHS P30ES07033 from the National Institute of Environmental Health Sciences ; 1 R03 CA106011 from the National Institutes of Health ; contract N01-CN-05230 from the National Cancer Institute ; and Fred Hutchinson Cancer Research Center. The authors declare they have no competing financial interests. Received 18 October 2004 ; accepted 17 March 2005. The full version of this article is available for free in HTML or PDF formats. |
