Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies

Wenxin Wan, Susan Peters, Lützen Portengen, Ann Olsson, Joachim Schüz, Wolfgang Ahrens, Miriam Schejbalova, Paolo Boffetta, Thomas Behrens, Thomas Brüning, Benjamin Kendzia, Dario Consonni, Paul A. Demers, Eleonóra Fabiánová, Guillermo Fernández-Tardón, John K. Field, Francesco Forastiere, Lenka Foretova, Pascal Guénel, Per GustavssonKarl Heinz Jöckel, Stefan Karrasch, Maria Teresa Landi, Jolanta Lissowska, Christine Barul, Dana Mates, John R. McLaughlin, Franco Merletti, Enrica Migliore, Lorenzo Richiardi, Tamás Pándics, Hermann Pohlabeln, Jack Siemiatycki, Beata Świątkowska, Heinz Erich Wichmann, David Zaridze, Calvin Ge, Kurt Straif, Hans Kromhout, Roel Vermeulen

Research output: Contribution to journalArticlepeer-review

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Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Original languageEnglish
Pages (from-to)185-196
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number2
StatePublished - 15 Jan 2024
Externally publishedYes


  • benzene
  • lung cancer
  • occupational exposure


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