Temporal Variation in the Association between Benzene and Leukemia Mortality

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 ≥ 20 years after exposure. Leukemia was more strongly associated with benzene exposures accrued at ≥ 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.