Air Pollution and Neighborhood Stressors as Determinants of Non-Small Cell Lung Cancer (NSCLC) Mutation Patterns and Recurrence

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death in the United States. Certain populations, such as non-Hispanic Black/African American (AA) individuals, are diagnosed at younger ages and experience less favorable outcomes. AA communities are also exposed to higher levels of environmental pollutants such as fine particulate matter (PM2.5). This study will investigate how long-term exposure to air pollution and neighborhood-level environmental stressors—including poverty indicators and limited access to resources—contributes to mutational patterns and disease progression in early-stage NSCLC in a high-risk population. We hypothesize that cumulative exposure to these stressors influences the timing and type of somatic mutations, ultimately affecting recurrence risk. We will conduct a study of 300 AA patients with stage I–II NSCLC from California, Georgia, and Detroit, integrating whole-genome sequencing (WGS) of tumor tissue with individualized environmental and geospatial exposure data. The aims of the study are to: (1) identify relationships between exposure history and mutational signatures (order and types of mutations); (2) assess how these exposures influence early recurrence (within 2 years post-surgery); and (3) compare the tumor genomics of never-smoking AA patients to the national Sherlock-Lung study, to evaluate the modifying effect of environmental stressors. This research will generate insights into how external exposures influence NSCLC biology and outcomes and may inform risk stratification and early detection strategies tailored to individuals experiencing elevated environmental exposures.