Occupational silica exposure has been demonstrated to cause both lung cancer and silicosis. However, it is unclear how the two disease processes interact and whether there is elevated lung cancer risk among those suffering from silicosis. We attempt to unravel the relative contributions of workplace exposure to the two processes using mediation analysis.
We estimate the direct effect of silica exposure on lung cancer: the portion of the effect of occupational silica exposure on lung cancer that does not pass through silicosis. The extent to which this differs from the total effect indicates the degree to which the disease processes are distinct from each other.
Among a cohort of 2,342 diatomaceous earth miners with measured exposures to crystalline silica, followed between 1942 and 2011, 113 (4%) died of lung cancer during follow-up. There were a total of 84 cases of silicosis diagnosed by radiologic analysis, of which 7 (8%) subsequently died from lung cancer.
We estimated the associations between cumulative silica exposure and death from lung cancer using a pooled logistic model, which returned odds ratios of 2.26 (95% CI: 1.02, 4.91), 2.85 (95% CI: 1.57, 4.19) and 2.27 (95% CI: 1.31, 4.19) at the second, third and fourth quartiles of silica exposure (relative to the first) when uncontrolled for silicosis. In an identical model that controls for diagnosis of silicosis, the corresponding ratios were 2.27 (95% CI: 1.03, 4.93), 2.91 (95% CI: 1.03, 4.94), and 2.39 (95% CI: 1.61, 5.55), indicating that the direct effect of silica exposure dominates the indirect pathway via silicosis. Future analyses will estimate the controlled direct effect of silica exposure using longitudinal targeted maximum likelihood estimation.
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