Temporal variation in the association between benzene and leukemia mortality

Environ Health Perspect. 2008 Mar;116(3):370-4. doi: 10.1289/ehp.10841.


Background: Benzene is a human carcinogen. Exposure to benzene occurs in occupational and environmental settings.

Objective: I evaluated variation in benzene-related leukemia with age at exposure and time since exposure.

Methods: I evaluated data from a cohort of 1,845 rubber hydrochloride workers. Benzene exposure-leukemia mortality trends were estimated by applying proportional hazards regression methods. Temporal variation in the impact of benzene on leukemia rates was assessed via exposure time windows and fitting of a multistage cancer model.

Results: The association between leukemia mortality and benzene exposures was of greatest magnitude in the 10 years immediately after exposure [relative rate (RR) at 10 ppm-years = 1.19; 95% confidence interval (CI), 1.10-1.29]; the association was of smaller magnitude in the period 10 to < 20 years after exposure (RR at 10 ppm-years = 1.05; 95% CI, 0.97-1.13); and there was no evidence of association > or = 20 years after exposure. Leukemia was more strongly associated with benzene exposures accrued at > or = 45 years of age (RR at 10 ppm-years = 1.11; 95% CI, 1.04-1.17) than with exposures accrued at younger ages (RR at 10 ppm-years = 1.01; 95% CI, 0.92-1.09). Jointly, these temporal effects can be efficiently modeled as a multistage process in which benzene exposure affects the penultimate stage in disease induction.

Conclusions: Further attention should be given to evaluating the susceptibility of older workers to benzene-induced leukemia.

Keywords: Ohio; benzene; cohort study; leukemia; mortality.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Benzene / toxicity*
  • Carcinogens, Environmental / toxicity*
  • Chemical Industry
  • Cohort Studies
  • Female
  • Humans
  • Leukemia / chemically induced
  • Leukemia / mortality*
  • Male
  • Middle Aged
  • Occupational Diseases / chemically induced
  • Occupational Diseases / mortality*
  • Occupational Exposure / adverse effects*
  • Time Factors


  • Carcinogens, Environmental
  • Benzene