Abstract Rationale Occupational silica exposure is a well-established risk factor for lung cancer. Silica can also be inhaled as a major component of volcanic ash and windblown soils, particularly Asian dust in East Asia, which are natural sources of particulate matter ≤2.5 μm (PM2.5). Exposure to PM2.5, which comprises various components, has been implicated in epidermal growth factor receptor (EGFR)-driven lung cancer development. We therefore investigated whether non-occupational inhalation of silica particles is associated with the EGFR mutation status of lung adenocarcinoma. Methods We conducted a retrospective cross-sectional study of consecutive patients with surgically resected lung adenocarcinoma who were tested for EGFR mutations between 2020 and 2022. Silica deposits in hematoxylin and eosin-stained sections of resected lung tissue were visualized under a polarizing microscope. To quantify the degree of silica deposits in each case, the total number of silica particles in 20 microscopic fields was counted. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value for silica deposition levels predicting EGFR mutations. Patients were categorized into high- and low-silica groups based on this cutoff value. We compared EGFR mutation profiles between the two groups and performed logistic regression model analysis to identify independent predictors. Results Of the 174 patients, only three had an occupational silica-exposure history. A significantly positive correlation was found between the number of silica deposits and age (r = 0.324, P 0.001). The median numbers of silica deposits were 26.0 and 9.0 particles in patients with EGFR mutations and with EGFR wild-type, respectively (P 0.001). EGFR mutations were detected in 66.7% and 30.4% of participants in the high- (n = 72) and low-silica groups (n = 102), respectively (P 0.001) (see the Figure below). The Cochran-Armitage trend test showed a significant linear trend for higher silica deposition with an increasing prevalence of EGFR mutations (P 0.001). Multivariate analysis revealed that high silica deposition (adjusted odds ratio, 3.20; 95% confidence interval CI, 1.49-6.88; P = 0.003) and never-smoker (adjusted odds ratio, 3.95; 95%CI, 1.65-9.47; P = 0.002) were independently associated with EGFR mutations. Conclusion Silica can be deposited in the lungs even without occupational exposure and is associated with EGFR-mutant lung adenocarcinoma. These findings suggest that environmental silica inhalation in daily life may play a role in EGFR-driven lung cancer. This abstract is funded by: JSPS KAKENHI Grant Number 25K11455
Hamada et al. (Fri,) studied this question.