Silicosis and Progressive Massive Fibrosis (PMF) are chronic interstitial lung diseases with a complex etiology that can occur after cumulative dust exposure. A large number of mediators such as cytokines, antioxidants and growth factors have been implicated in the pathogenesis of experimental and human pulmonary fibrosis. Common functional polymorphisms in these genes have been shown to influence individual susceptibility against various lung pathologies including, cancer, asthma, and chronic obstructive pulmonary disease. In light of this, we investigated associations between cytokine, antioxidant and fibrogenic gene variations and the development and severity of dust-induced pulmonary fibrosis in excoal miners with silicosis and PMF. A significant associationwas found between silicosis and the TNF-238, TNF-308 and IL-1RA +2018 variants. Also, an association between accelerated decline in lung function and genetic variations in cytokine genes were investigated in firefighters. There is a broad range of rates of longitudinal decline in lung function among firefighters, and this cannot be explained with differential occupational smoke exposure. Genetic differences in pulmonary response to respiratory toxicants likely play a role in determining the rate of longitudinal decline. Our results showed that the presence of IL-1+3953, IL-1RA +2018 and TNF-308 variants are associated with the decline rate of lung function as measured by FEV1. These findings suggest that specific variants of cytokine genes may influence individual susceptibility to occupational pulmonary diseases.