Combined Occupational Exposure to Lead and Other Metals and Risk of Lung Cancer
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Keywords
lead, arsenic , cadmium , lung cancer , interaction , co-exposure
Abstract
Background: The evidence linking occupational exposure to lead and cancer in humans is suggestive. Existing studies examine individual exposure to lead, ignoring the potential joint effects of mixed metal exposure. Methods:We analyzed the data of a case-control study of lung cancer conducted in seven European countries and comprising 2,861 cases and 2,936 controls, with a detailed assessment of occupational exposure to arsenic, cadmium, chromium (VI), and lead, to estimate the odds ratio (OR) of lung cancer for combined exposure to lead and these other carcinogenic metals, after adjustment for potential confounders. Results: The results suggested a synergism between lead and arsenic or cadmium: ORs were around 1.0 for lead alone and above 2.0 for combined exposure. No interaction was suggested between lead and chromium (VI). Conclusion: Our results provide suggestive evidence of a possible interaction between occupational exposure to lead, arsenic, or cadmium and lung cancer risk, and highlight the importance of considering mixed metal exposures in occupational epidemiology.
References
2. Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol. 2023;20(9):624-639.
3. de Sousa Alves M, de Carvalho LSS, Nogueira LT, Furtado SAS. Occupational hazards and the develop-ment of lung cancer: an analysis of exposures and their implications for worker health. Rev Bras Med Trab. 2025;23(3):e20251417.
4. International Agency for Research on Cancer. Arsenic, Metals, Fibres, and Dusts. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 100C. Lyon, France: IARC; 2012.
5. Straif K, Benbrahim-Tallaa L, Baan R, et al; WHO International Agency for Research on Cancer Mono-graph Working Group. A review of human carcinogens–Part C: metals, arsenic, dusts, and fibres. Lancet Oncol. 2009;10(5):453-4.
6. Chen C, Xun P, Nishijo M, He K. Cadmium exposure and risk of lung cancer: a meta-analysis of cohort and case-control studies among general and occupational populations. J Expo Sci Environ Epidemiol. 2016;26(5):437-44.
7. Beveridge R, Pintos J, Parent ME, Asselin J, Siemiatycki J. Lung cancer risk associated with occupa-tional exposure to nickel, chromium VI, and cadmium in two population-based case-control studies in Montreal. Am J Ind Med. 2010;53(5):476-85.
8. 't Mannetje A, Bencko V, Brennan P, et al. Occupational exposure to metal compounds and lung cancer. Results from a multi-center case-control study in Central/Eastern Europe and UK. Cancer Causes Control. 2011;22(12):1669-80.
9. International Agency for Research on Cancer. Inorganic and Organic Lead Compounds. IARC Mono-graphs on the Evaluation of Carcinogenic Risks to Humans, Volume 87. Lyon, France: IARC; 2006.
10. Fu H, Boffetta P. Cancer and occupational exposure to inorganic lead compounds: a meta-analysis of published data. Occup Environ Med. 1995;52(2):73-81.
11. Lundström NG, Nordberg G, Englyst V, et al. Cumulative lead exposure in relation to mortality and lung cancer morbidity in a cohort of primary smelter workers. Scand J Work Environ Health. 1997;23(1):24-30.
12. Anttila A, Uuksulainen S, Rantanen M, Sallmén M. Lung cancer incidence among workers biologically monitored for occupational exposure to lead: a cohort study. Scand J Work Environ Health. 2022;48(7):540-548.
13. Wynant W, Siemiatycki J, Parent MÉ, Rousseau MC. Occupational exposure to lead and lung cancer: results from two case-control studies in Montreal, Canada. Occup Environ Med. 2013;70(3):164-70.
14. Wild P, Bourgkard E, Paris C. Lung cancer and exposure to metals: the epidemiological evidence. Methods Mol Biol. 2009;472:139-67.
15. Madden EF. The role of combined metal interactions in metal carcinogenesis: a review. Rev Environ Health. 2003;18(2):91-109.
16. Zhu Y, Costa M. Metals and molecular carcinogenesis. Carcinogenesis. 2020;41(9):1161-1172.
17. Olsson A, Bouaoun L, Schüz J, et al. Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY). Environ Health Perspect. 2024;132(1):17005.
18. Boffetta P, Zaridze D, Świątkowska B, et al. Combined occupational exposure to carcinogenic met-als/metalloids and risk of lung cancer. Front. Oncol. 2026;16:1772676. Doi: 10.3389/fonc.2026.1772676
19. ‘Mannetje A', Fevotte J, Fletcher T, et al. Assessing exposure misclassification by expert assessment in multicenter occupational studies. Epidemiology. 2003;14(5):585-92.
20. Siemiatycki J, Wacholder S, Richardson L, Dewar R, Gérin M. Discovering carcinogens in the occupa-tional environment: Methods of data collection and analysis of a large case-referent monitoring sys-tem. Scand J Work Environ Health. 1987;13(6), 486-492.
21. VanderWeele TJ, Knol MJ. A tutorial on interaction. Epidemiol Meth, 2014;3:33-72.
22. Salnikow K, Zhitkovich A. Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcino-genesis: nickel, arsenic, and chromium. Chem Res Toxicol. 2008;21(1):28-44.
23. Talha T, Zahoor U, Azhar S, et al. Oxidative stress pathways in cancer: lessons learned from heavy metal exposures: oxidative stress and heavy metals. J Health Rehabil Res. 2024;4(3):1-6.
24. Liu X, Wu J, Shi W, Shi W, Liu H, Wu X. Lead Induces Genotoxicity via Oxidative Stress and Promoter Methylation of DNA Repair Genes in Human Lymphoblastoid TK6 Cells. Med Sci Monit. 2018;24:4295-4304.
25. Hemmaphan S, Bordeerat NK. Genotoxic Effects of Lead and Their Impact on the Expression of DNA Repair Genes. Int J Environ Res Public Health. 2022;19(7):4307.
26. Bailey J, McFarlane S, Amarakoon I. Heavy metal carcinogenicity: a scoping review of observational & experimental evidence. Front Oncol. 2025;15:1569816.
27. Agency for Toxic Substances and Disease Registry. Interaction profile for arsenic, cadmium, chro-mium, and lead. Atlanta (GA): U.S. Department of Health and Human Services, Public Health Service; 2004. Available from: https://www.atsdr.cdc.gov/interaction-profiles/about/arsenic-cadmium-chromium-lead.html
28. Balali-Mood M, Naseri K, Tahergorabi Z, Khazdair MR, Sadeghi M. Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic. Front Pharmacol. 2021;12:643972.
29. Elkin ER, Higgins C, Aung MT, Bakulski KM. Metals Exposures and DNA Methylation: Current Evidence and Future Directions. Curr Environ Health Rep. 2022;9(4):673-696.
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