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Case-control investigation of occupational exposure to chlorinated solvents and non-Hodgkin’s lymphoma
  1. Catherine L Callahan1,
  2. Patricia A Stewart2,
  3. Melissa C Friesen1,
  4. Sarah Locke1,
  5. Anneclaire J De Roos3,
  6. James R Cerhan4,
  7. Richard K Severson5,
  8. Nathaniel Rothman1,
  9. Mark P Purdue1
  1. 1Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
  2. 2Stewart Exposure Assessments, LLC, Arlington, Virginia, USA
  3. 3Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA
  4. 4Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
  5. 5Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USA
  1. Correspondence to Dr Catherine L Callahan, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850 USA; catherine.callahan{at}


Objectives Although many studies have investigated the association between trichloroethylene (TCE) exposure and non-Hodgkin’s lymphoma (NHL), less is known about other chlorinated solvents. We extended our previous analysis of occupational TCE exposure in a multicentre population-based case-control study of NHL to investigate associations with five additional chlorinated solvents: 1,1,1,-trichloroethane, carbon tetrachloride, chloroform, methylene chloride and perchloroethylene.

Methods Cases (n=1189) and controls (n=982) provided detailed information on their occupational histories and workplace exposure to chlorinated solvents for selected occupations using job-specific interview modules. An industrial hygienist used this information and a review of the literature to assess occupational exposure to chlorinated solvents. We computed ORs and 95% CIs for different exposure metrics, with the unexposed group as the referent. We also computed ORs by NHL subtype.

Results High cumulative hours exposed to carbon tetrachloride was associated with NHL (>520 hours: OR 1.9; 95% CI 1.0 to 3.6; Ptrend=0.04). This association remained after restricting to jobs with high-intensity exposure (OR 2.0; 95% CI 1.1 to 3.8; P=0.03) and ≥90% exposure probability (OR 2.1; 95% CI 1.0 to 4.3; P=0.03), adjusting for TCE (OR 2.1; 95% CI 1.0– to 4.1; P=0.04) and incorporating a 15-year lag (OR 1.9; 95% CI 1.0 to 3.6; P=0.06). The other evaluated chlorinated solvents were not associated with NHL.

Conclusions This is the first study using high-quality quantitative exposure assessment methods to identify a statistically significant elevated association between occupational exposure to carbon tetrachloride and NHL. Our findings, although limited by a small number of exposed cases, offer evidence that carbon tetrachloride may be a lymphomagen.

  • epidemiology
  • cancer
  • solvents

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  • Contributors PAS, AJDR, JRC, RKS and NR contributed to the design, enrolment and/or data collection of the case-control study. PAS, MPP, MCF and SL contributed to the exposure assessment. MPP and CLC conducted the statistical analysis for this project. MPP and CLC drafted the manuscript. All authors contributed to the writing of the manuscript.

  • Funding This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, with Public Health Service contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010 and N02-PC-71105.

  • Competing interests PAS is employed by Stewart Exposure Assessments, LLC (Arlington, Virginia, USA).

  • Patient consent Not required.

  • Ethics approval The study was approved by the institutional review boards at the NCI and the participating institutions.

  • Provenance and peer review Not commissioned; externally peer reviewed.