Research Question and Objective
Thoracic surgical diseases, including lung and esophageal cancers, cause significant global mortality, with lung cancer claiming 1.8 million lives yearly. Aging populations and environmental exposures-air pollution, tobacco smoke, and occupational carcinogens-interact with genetic susceptibility to drive pathogenesis, yet molecular mechanisms remain unclear. This study leverages the UK Biobank’s multi-omics data, environmental records, and clinical outcomes to identify novel biomarkers and modifiable risks by integrating genomic, proteomic, and pollution exposure profiles. We focus on causal pathways linking pollutants like particulate matter to somatic mutations, chronic inflammation, and immune dysfunction that fuel tumor progression and surgical complications.
Scientific Rationale
The rationale hinges on environmental stressors inducing genomic instability, metabolic reprogramming, and proteomic shifts, such as dysregulated lipid metabolites and immune signaling. While germline variants predict susceptibility, real-time molecular responses to pollutants are poorly understood. By synthesizing tumor mutation data, immune proteomics, and pollution metrics, this study maps how environmental triggers and genetic risks converge to shape outcomes like metastasis and recurrence. Translational impact lies in precision risk models combining genetic, proteomic, and environmental data to enable early detection and personalized interventions. This framework advances thoracic surgery research by targeting actionable pathways for risk mitigation and tailored therapies aligned with individual molecular and environmental contexts.
