title: Myelodysplastic syndrome and benzene exposure among petroleum workers: an international pooled analysis.
abstract: BACKGROUND
  Benzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers.
  
  
  METHODS
  We updated three nested case-control studies from Australia, Canada, and the United Kingdom with new incident LH cancers among petroleum distribution workers through December 31, 2006, and pooled 370 potential case subjects and 1587 matched LH cancer-free control subjects. Quantitative benzene exposure in parts per million (ppm) was blindly reconstructed using historical monitoring data, and exposure certainty was scored as high, medium, or low. Two hematopathologists assigned diagnoses and scored the certainty of diagnosis as high, medium, or low. Dose-response relationships were examined for five LH cancers, including the three most common leukemia cell-types (AML, chronic myeloid leukemia [CML], and chronic lymphoid leukemia [CLL]) and two myeloid tumors (myelodysplastic syndrome [MDS] and myeloproliferative disease [MPD]). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, controlling for age, sex, and time period.
  
  
  RESULTS
  Cumulative benzene exposure showed a monotonic dose-response relationship with MDS (highest vs lowest tertile, >2.93 vs ≤0.348 ppm-years, OR = 4.33, 95% CI = 1.31 to 14.3). For peak benezene exposures (>3 ppm), the risk of MDS was increased in high and medium certainty diagnoses (peak exposure vs no peak exposure, OR = 6.32, 95% CI = 1.32 to 30.2) and in workers having the highest exposure certainty (peak exposure vs no peak exposure, OR = 5.74, 95% CI = 1.05 to 31.2). There was little evidence of dose-response relationships for AML, CLL, CML, or MPD.
  
  
  CONCLUSIONS
  Relatively low-level exposure to benzene experienced by petroleum distribution workers was associated with an increased risk of MDS, but not AML, suggesting that MDS may be the more relevant health risk for lower exposures.
authors.affiliation: Occupational and Public Health Division, ExxonMobil Biomedical Sciences, Inc, 1545 US Highway 22 East, Annandale, NJ 08801-3059, USA. a.r.schnatter@exxonmobil.com
authors.forename: A Robert
authors.initials: AR
authors.lastname: Schnatter
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Glass
authors.forename: Gong
authors.initials: G
authors.lastname: Tang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Irons
authors.forename: Lesley
authors.initials: L
authors.lastname: Rushton
mesh_terms: D000328:Adult; D001315:Australia / Q000453:epidemiology; D001554:Benzene / Q000633:toxicity*; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D019652:Extraction and Processing Industry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000209:etiology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000453:epidemiology / Q000209:etiology; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D009196:Myeloproliferative Disorders / Q000453:epidemiology / Q000209:etiology; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology*; D016273:Occupational Exposure / Q000009:adverse effects*; D016017:Odds Ratio; D010578:Petroleum; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D010578:Petroleum; D001554:Benzene