title: An exploratory case-only analysis of gene-hazardous air pollutant interactions and the risk of childhood medulloblastoma.
abstract: BACKGROUND
  There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants; however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk.
  
  
  METHODS
  We conducted a case-only study to evaluate census tract-level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children's Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the US EPA's 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case-only odds ratios and 95% confidence intervals (CIs).
  
  
  RESULTS
  There were 11 significant gene-environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04).
  
  
  CONCLUSIONS
  This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies.
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Lee
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Okcu
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Bondy
authors.forename: Michael E
authors.initials: ME
authors.lastname: Scheurer
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects*; D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D002528:Cerebellar Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D002648:Child; D004260:DNA Repair / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000009:adverse effects*; D008297:Male; D008527:Medulloblastoma / Q000139:chemically induced* / Q000235:genetics*; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D018242:Neuroectodermal Tumors, Primitive / Q000139:chemically induced* / Q000235:genetics*; D012997:Solvents / Q000009:adverse effects
chemical_list: D000393:Air Pollutants; D000395:Air Pollutants, Occupational; D006843:Hydrocarbons, Chlorinated; D012997:Solvents