Occupational Benzene Exposure and Lung Cancer in Human Studies: A Systematic Review and Meta-Analysis

BACKGROUND: Benzene is classified as carcinogenic to humans based on evidence that benzene causes acute myeloid leukemia. However, there is limited evidence that benzene causes lung cancer. OBJECTIVES: We performed a systematic review, quality assessment, and meta-analysis of published cohort and case-control studies on the association between occupational benzene exposure and lung cancer risk. METHODS: We reviewed the relevant human epidemiological studies from PubMed and Embase databases to 19 August 2024. Data extraction included study characteristics, effect estimates, and exposure assessment details. Two investigators independently evaluated study quality using the Newcastle-Ottawa scale (NOS) framework and exposure assessment quality based on a priori criteria. Six risk of bias (ROB) domains were constructed from the NOS criteria to identify and quantify possible biases and their impacts on parameter estimates. Meta-analysis relative risk (pooled RR) and associated confidence intervals were calculated using random-effects models, and a flexible exposure-response meta-regression was fitted to assess the shape of the association. Subgroup analyses were conducted to explore the consistency of results. RESULTS: Of 252 articles identified, 13 studies covering 366,975 participants (17,030 lung cancer cases) were included in our analysis. The meta-analysis of ever occupational benzene exposure showed an elevated risk of lung cancer (pooled formula presented ; 95% CI: 1.03, 1.27; formula presented ). Subgroup analyses revealed that larger pooled RRs in studies based on highly exposed groups had higher overall quality and better exposure assessments and included both males and females (as opposed to only males). A positive linear trend was observed in the exposure-response meta-analysis. DISCUSSION: Our meta-analysis supports an association between occupational benzene exposure and an increased risk of lung cancer. https://doi.org/10.1289/EHP15086.