Silicosis and lung cancer: current perspectives

Takashi Sato,1 Takeshi Shimosato,2 Dennis M Klinman3 1Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan; 2Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Shinshu University, Nagano 399-4598, Japan; 3Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA Abstract: “Silica” refers to crystalline particles formed by the combination of silicon with oxygen. Inhalation of silica particles promotes the development of pulmonary fibrosis that over prolonged periods increases the risk of lung cancer. The International Agency for Research on Cancer (IARC) classified crystalline silica as a human carcinogen in 1997. This categorization was questioned due to 1) the absence of dose–response findings, 2) the presence of confounding variables that complicated interpretation of the data and 3) potential selection bias for compensated silicosis. Yet, recent epidemiologic studies strongly support the conclusion that silica exposure increases the risk of lung cancer in humans independent of confounding factors including cigarette smoke. Based on this evidence, the US Occupational Safety and Health Administration (OSHA) lowered the occupational exposure limit for crystalline silica from 0.1 to 0.05 mg/m3 in 2013. Further supporting the human epidemiologic data, murine models show that chronic silicosis is associated with an increased risk of lung cancer. In animals, the initial inflammation induced by silica exposure is followed by the development of an immunosuppressive microenvironment that supports the growth of lung tumors. This work will review our current knowledge of silica-associated lung cancers, highlighting how recent mechanistic insights support the use of cutting-edge approaches to diagnose and treat silica-related lung cancer. Keywords: silicosis, lung cancer, inflammation, fibrosis, occupational lung diseas