Academic journal article Environmental Health Perspectives

Childhood Brain Tumors, Residential Insecticide Exposure, and Pesticide Metabolism Genes

Academic journal article Environmental Health Perspectives

Childhood Brain Tumors, Residential Insecticide Exposure, and Pesticide Metabolism Genes

Article excerpt

BACKGROUND: Insecticides that target the nervous system may play a role in the development of childhood brain tumors (CBTs). Constitutive genetic variation affects metabolism of these chemicals.

METHODS; We analyzed population-based case-control data to examine whether CBT is associated with the functional genetic polymorphisms [PON1.sub.C-108T], [PON1.sub.C-Q192R], [PON1.sub.L55M][BCHE.sub.A539T], [FMO1.sub.C-9536A], [FMO3.sub.E158K], [ALDH3A1.sub.S134A],, and GSTT1 (null). DNA was obtained from newborn screening archives for 201 cases and 285 controls, [less than or equal to] 10 years of age, and born in California or Washington State between 1978 and 1990. Conception-to-diagnosis home insecticide treatment history was ascertained by interview.

RESULTS: We observed no biologically plausible main effects for any of the metabolic polymorphisms with CBT risk. However, we observed strong interactions between genotype and insecticide exposure during childhood. Among exposed children, CBT risk increased per [PON1.sub.-108T] allele [odds ratio (OR) = 1.8; 95% confidence interval (CI), 1.1-3.0] and [FMO1.sub.-9536A] (*6) allele (OR = 2.7; 95% CI, 1.2-5.9), whereas among children never exposed, CBT risk was not increased (PON1: OR = 0.7; 95% CI, 0.5-1.0, interaction p = 0.005; FMO1 OR = 1.0; 95% CI, 0.6-1.6, interaction p = 0.009). We observed a similar but statistically nonsignificant interaction between childhood exposure and [BCHE.sub.A539T] (interaction p = 0.08). These interactions were present among both Hispanic and non-Hispanic white children.

CONCLUSION: Based on known effects of these variants, these results suggest that exposure in childhood to organophosphorus and perhaps to carbamate insecticides in combination with a reduced ability to detoxify them may be associated with CBT. Confirmation in other studies is required.

KEY WORDS: acetylcholinesterase inhibition, childhood cancer, children, gene-environment interaction, insecticides, pesticides, xenobiotic metabolism. Environ Health Perspect 118:144-149 (2010). doi:10.1289/ehp.0901226 available via http://dx.doi.org/ [Online 5 October 2009]

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Both environmental exposure and genes affect childhood brain tumor (CBT) development. Ionizing radiation to the head and selected heritable syndromes are established risk factors (Fisher et al. 2007). However, these account for only a small proportion of CBT cases. Several epidemiologic studies suggest pesticides might be associated with CBT (Infante-Rivard and Weichenthal 2007), but most relied on retrospective questionnaire data with little detail. One study that considered the type and timing of pesticide exposure observed an increased risk of CBT with prenatal exposure to flea/tick products, but not herbicides, fungicides, or molluscicides (Pogoda and Preston-Martin 1997). The specificity of this finding is interesting because the major classes of insecticides--organophosphorus (OP), carbamate, organochlorine (OC), and pyrethrin/ pyrethroid--readily cross the blood-brain barrier and target the nervous system, whereas pesticides aimed at plants and fungi inherently rely on different mechanisms of action.

Because constitutive genetic variation influences insecticide metabolism, we previously examined whether CBT is associated with two single nucleotide polymorphisms (SNPs) in the gene that codes for paraoxonase (PON1) (Searles Nielsen et al. 2005). We observed no association between CBT and the single coding region SNP [PON1.sub.Q192R] but a strong dose-response relationship between CBT and [PON1.sub.C-108T], a promoter-region SNP associated with enzyme levels. CBT risk was increased among children who presumably had a reduced ability to detoxify chlorpyrifos and diazinon, the most common residential insecticides for many years, and this association was restricted to children whose homes had been chemically treated for insects. Here we examine these SNPs and six additional genetic polymorphisms that affect insecticide metabolism using an expanded number of cases and controls born in Washington State and California. …

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