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

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_C-108T, PON1_Q192R, PON _1L55M, BCHE_A539T, FMO1_C-9536A, FMO3 _E158K, ALDH3A1_S134A, 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 BCHE_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.