Int Arch Occup Environ Health (2009) 82:867–875 DOI 10.1007/s00420-008-0386-1 123 ORIGINAL ARTICLE Major histopathological patterns of lung cancer related to arsenic exposure in German uranium miners Dirk Taeger · Georg Johnen · Thorsten Wiethege · Soile Tapio · Matthias Möhner · Horst Wesch · Andrea Tannapfel · Klaus-Michael Müller · Thomas Brüning · Beate Pesch Received: 9 May 2008 / Accepted: 3 November 2008 / Published online: 20 November 2008  Springer-Verlag 2008 Abstract Objective The mechanisms of action of arsenic in the development of lung cancer are still not yet elucidated. Considering the relationship between arsenic and squamous cell carcinomas of the skin, we hypothesized that arsenic exposure may be more closely associated with squamous cell carcinoma of the lung. Methods A comprehensive histopathological database and a detailed job-exposure matrix developed for former German uranium miners with exposure to arsenic, radon, and quartz were analyzed to quantitatively assess the eVect of arsenic regarding cell type of lung cancer. The distribu- tions of major lung cancer cell types in 1,786 German ura- nium miners were associated with levels of arsenic exposure under control for the other lung carcinogens. To evaluate the arsenic eVects in association with a frequent occupational lung disease in miners stratiWcation by silico- sis was performed. Results There was an arsenic-related increase of the pro- portion of squamous cell carcinoma of the lung but restricted to miners without silicosis. The increase was found at all levels of co-exposure to radon and quartz dust. In miners with silicosis, the proportion of adenocarcinoma increased with rising arsenic exposure. Arsenic exposure was associated with non-small cell lung cancer. Silicosis turned out as major determinant of the cell type related with arsenic. Conclusion These results indicate a cell type characteris- tic eVect of arsenic in the development of lung cancer. Keywords Lung cancer · Arsenic · Uranium mining · Histology · Silicosis Introduction Between 1946 and 1990, about 230,000 tons of uranium were mined by the former WISMUT company in East Ger- many for the Soviet nuclear program (Wesch et al. 1999). The miners were not only exposed to high doses of ionizing radiation and crystalline silica but in many mines also to arsenic. An arsenic content of up to 8% in the ore together with lacking protective measures under Soviet supervision posed a serious health hazard for many workers. D. Taeger · G. Johnen · T. Wiethege · T. Brüning · B. Pesch BGFA—Research Institute of Occupational Medicine, German Social Accident Insurance, Ruhr University, Bochum, Germany S. Tapio Federal OYce for Radiation Protection (BfS), Neuherberg, Germany S. Tapio Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany M. Möhner Federal Institute for Occupational Safety and Health (BAuA), Berlin, Germany H. Wesch Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany A. Tannapfel · K.-M. Müller Institute of Pathology, Berufsgenossenschaftliche Kliniken Bergmannsheil, Ruhr University, Bochum, Germany D. Taeger (&) BGFA—Forschungsinstitut für Arbeitsmedizin der DGUV, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany e-mail: taeger@bgfa.de