Open Access Highly Accessed Open Badges Research

Exposure to benzene at work and the risk of leukemia: a systematic review and meta-analysis

Abdul Khalade1, Maritta S Jaakkola2, Eero Pukkala34 and Jouni JK Jaakkola15*

Author Affiliations

1 Institute of Occupational and Environmental Medicine, University of Birmingham, UK

2 Center for Environmental and Respiratory Health Research, Respiratory Medicine Unit, Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, P.O. B. 5000, 90014 Oulu, Finland

3 Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Pieni Roobertinkatu 9, Helsinki, Finland

4 School of Public Health, University of Tampere, Tampere, Finland

5 Center for Environmental and Respiratory Health Research, Institute of Health Sciences, University of Oulu, P.O. B. 5000, 90014 Oulu, Finland

For all author emails, please log on.

Environmental Health 2010, 9:31  doi:10.1186/1476-069X-9-31

Published: 28 June 2010



A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).


A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size).


In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant.


Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML.