Childhood brain tumors, residential insecticide exposure, and pesticide metabolism genes

Susan Searles Nielsen, Roberta McKean-Cowdin, Federico M. Farin, Elizabeth A. Holly, Susan Preston-Martin, Beth A. Mueller

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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 PON1C-108T, PON1Q192R, PON 1L55M, BCHEA539T, FMO1C-9536A, FMO3 E158K, ALDH3A1S134A, and GSTT1 (null). DNA was obtained from newborn screening archives for 201 cases and 285 controls, ≤ 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 PON1-108T allele [odds ratio (OR) = 1.8; 95% confidence interval (CI), 1.1-3.0] and FMO1-9536A (*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 BCHEA539T (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.

Original languageEnglish
Pages (from-to)144-149
Number of pages6
JournalEnvironmental Health Perspectives
Volume118
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Acetylcholinesterase inhibition
  • Childhood cancer
  • Children
  • Gene-environment interaction
  • Insecticides
  • Pesticides
  • Xenobiotic metabolism

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