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The Upper Midwest Health Study: gliomas and occupational exposure to chlorinated solvents
  1. Avima M Ruder1,
  2. James H Yiin1,
  3. Martha A Waters1,
  4. Tania Carreón1,
  5. Misty J Hein1,
  6. Mary A Butler1,
  7. Geoffrey M Calvert1,
  8. Karen E Davis-King1,
  9. Paul A Schulte1,
  10. Jack S Mandel2,
  11. Roscoe F Morton3,
  12. Douglas J Reding4,
  13. Kenneth D Rosenman5,
  14. Patricia A Stewart6,
  15. the Brain Cancer Collaborative Study Group
  1. 1National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, Ohio, USA
  2. 2School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
  3. 3Mercy Medical Center, Des Moines, Iowa, USA
  4. 4National Farm Medicine Center, Marshfield Clinic, Marshfield, Wisconsin, USA
  5. 5Department of Medicine, Michigan State University, East Lansing, Michigan, USA
  6. 6Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  1. Correspondence to Dr Avima M Ruder, Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Mailstop R-16, Cincinnati, OH 45226, USA; amr2{at}


Objectives 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.

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