title: Parental smoking and risk of childhood brain tumors by functional polymorphisms in polycyclic aromatic hydrocarbon metabolism genes.
abstract: BACKGROUND
  A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals.
  
  
  METHODS
  We assessed 9 functional polymorphisms in 6 genes that affect the metabolism of polycyclic aromatic hydrocarbons (PAH) to evaluate potential interactions with parental smoking during pregnancy in a population-based case-control study of childhood brain tumors. Cases (N = 202) were ≤10 years old, diagnosed from 1984-1991 and identified in three Surveillance, Epidemiology, and End Results (SEER) registries in the western U.S. Controls in the same regions (N = 286) were frequency matched by age, sex, and study center. DNA for genotyping was obtained from archived newborn dried blood spots.
  
  
  RESULTS
  We found positive interaction odds ratios (ORs) for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P(interaction) = 0.02; 0.10), such that children with the high-risk (greater PAH activation) genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. A dose-response pattern for paternal smoking was observed among children with the EPHX1 H139R high-risk genotype only (OR(no exposure) = 1.0; OR(≤3 hours/day) = 1.32, 95% CI: 0.52-3.34; OR(>3 hours/day )= 3.18, 95% CI: 0.92-11.0; P(trend )= 0.07).
  
  
  CONCLUSIONS
  Parental smoking during pregnancy may be a risk factor for childhood brain tumors among genetically susceptible children who more rapidly activate PAH in tobacco smoke.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, California, United States of America.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Barrington-Trimis
authors.forename: Susan
authors.initials: S
authors.lastname: Searles Nielsen
authors.forename: Susan
authors.initials: S
authors.lastname: Preston-Martin
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Holly
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Beth A
authors.initials: BA
authors.lastname: Mueller
authors.forename: Roberta
authors.initials: R
authors.lastname: McKean-Cowdin
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D011084:Polycyclic Aromatic Hydrocarbons