Air pollution, driver mutations, and survival in non-small cell lung cancer: insights from a high-altitude Hispanic cohort

Background: Lung cancer remains a critical global health concern, with a substantial fraction arising in never-smokers. Air pollution—including particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3)—has been implicated in lung carcinogenesis; however, studies linking these exposures to molecular biomarkers in Hispanic populations remain scarce. This study aimed to evaluate the association between exposure to air pollutants and oncogenic mutations in non-small cell lung cancer (NSCLC) in Hispanic patients in Bogotá. Methods: A retrospective cohort study was conducted on 205 Hispanic patients diagnosed with NSCLC between 2015 and 2022 at a quaternary care hospital in Bogotá, Colombia. Lung cancer driver mutations [epidermal growth factor receptor mutations (EGFRm), anaplastic lymphoma kinase (ALK) rearrangement, and programmed death-ligand 1 (PD-L1) expression] were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. The estimated individual-level exposure to air pollutants (PM2.5, PM10, NO2, SO2, O3, and CO) was assessed from Bogotá’s Air Monitoring Stations using an inverse distance weighted regression model. Adjusted logistic regression analyses evaluated associations between biomarkers and pollutants. Kaplan-Meier and Cox proportional hazards models examined survival outcomes. Results: Mean annual exposure to PM2.5 (15.9 µg/m3), PM10 (32.6 µg/m3), and NO2 (28.3 µg/m3) exceeded the thresholds recommended by the World Health Organization. EGFRm were identified in 24.9% of patients, ALK rearrangements in 12.2%, and PD-L1 expression ≥1% in 41.5% (≥50% in 5.4%). EGFRm was associated with increased exposure to PM2.5 and PM10 levels [PM2.5: odds ratio (OR) 2.49, 95% confidence interval (CI): 1.11–6.41; PM10: OR 1.54, 95% CI: 1.05–2.34]. NO2 was associated with increased PD-L1 expression (OR 1.83, 95% CI: 1.33–2.65). The 5-year overall survival (OS) rate was 29.0%. Increased exposure to PM2.5 [hazard ratio (HR) 1.72; 95% CI: 1.04–2.84] and SO2 (HR 1.69, 95% CI: 1.07–2.68) were associated with mortality. Conclusions: These results underscore the potential impact of air pollution on the molecular landscape and clinical outcomes of patients diagnosed with NSCLC, and they open new avenues for research in genetically admixed populations.