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 PON1C-108T, PON1Q192R, PON1L55M, BCHEA539T, FMO1C-9536A, FMO3E158K, ALDH3A1S134A, and GSTT1 (null). DNA was obtained from newborn screening archives for 201 cases and 285 controls, <or= 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.


CONCLUSIONS
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.
Searles Nielsen
Susan
S
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. snielsen@fhcrc.org
McKean-Cowdin
Roberta
R
Farin
Federico M
FM
Holly
Elizabeth A
EA
Preston-Martin
Susan
S
Mueller
Beth A
BA
D000444:Aldehyde Dehydrogenase / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics; D001932:Brain Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D010105:Oxygenases / Q000235:genetics; D010575:Pesticides / Q000493:pharmacokinetics* / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
D007306:Insecticides; D010575:Pesticides; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human