Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 118, Issue 1, Pages 144-149Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.0901226
Keywords
acetylcholinesterase inhibition; childhood cancer; children; gene-environment interaction; insecticides; pesticides; xenobiotic metabolism
Funding
- National Institutes of Health [R01 CA116724, R03 CA106011]
- National Institute of Environmental Health Sciences (NIEHS) [P30ES007033, 5P30ES07048, T32ES07262]
- National Cancer Institute [N01-CN-05230]
- Fred Hutchinson Cancer Research Center
- DIVISION OF CANCER PREVENTION AND CONTROL [N01CN005230] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [R03CA106011, R01CA116724] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007262, P30ES007033, P30ES007048] Funding Source: NIH RePORTER
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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), PON1(L55M), BCHEA539T, FMO1(C-9536A), FMO3(E158K), ALDH3A1(S134A), and GSM (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.
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