title: The Upper Midwest Health Study: gliomas and occupational exposure to chlorinated solvents.
abstract: OBJECTIVE
  Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents--carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1--trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites.
  
  
  RESULTS
  Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma.
  
  
  CONCLUSIONS
  We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.
authors.affiliation: National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, OH, USA. amr2@cdc.gov
authors.forename: Avima M
authors.initials: AM
authors.lastname: Ruder
authors.forename: James H
authors.initials: JH
authors.lastname: Yiin
authors.forename: Martha A
authors.initials: MA
authors.lastname: Waters
authors.forename: Tania
authors.initials: T
authors.lastname: Carreón
authors.forename: Misty J
authors.initials: MJ
authors.lastname: Hein
authors.forename: Mary A
authors.initials: MA
authors.lastname: Butler
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Calvert
authors.forename: Karen E
authors.initials: KE
authors.lastname: Davis-King
authors.forename: Paul A
authors.initials: PA
authors.lastname: Schulte
authors.forename: Jack S
authors.initials: JS
authors.lastname: Mandel
authors.forename: Roscoe F
authors.initials: RF
authors.lastname: Morton
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Reding
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Rosenman
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005910:Glioma / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D015146:Midwestern United States / Q000453:epidemiology; D016273:Occupational Exposure / Q000009:adverse effects*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D012997:Solvents / Q000633:toxicity*; D055815:Young Adult
chemical_list: D006843:Hydrocarbons, Chlorinated; D012997:Solvents; D005982:Glutathione Transferase