Air pollution exposure and breast cancer: a network toxicology-based multiscale analysis identifies CCNE2 as a key molecular mediator

Air pollution is a major environmental health risk and has been classified as a Group 1 carcinogen. While its link to lung cancer is well established, the molecular mechanisms connecting air pollution to breast cancer are not fully understood. In this study, we used a network toxicology approach to investigate the relationship between seven common air pollutants and breast cancer. Target genes associated with these pollutants were identified from public databases and compared with genes linked to breast cancer. Forty-eight core genes were found as potential mediators. Functional enrichment analyses revealed that these genes were involved in xenobiotic metabolism, DNA damage response, cell cycle regulation, and inflammatory pathways such as PI3K–Akt and TNF signaling. Protein–protein interaction networks highlighted CCNE2 as a central hub gene, and high expression of CCNE2 was associated with poorer overall survival in breast cancer patients. Molecular docking suggested that CCNE2 can stably bind to aromatic pollutants, especially toluene. Single-cell RNA sequencing and immunohistochemistry analyses showed that CCNE2 expression is mainly localized in breast cancer epithelial cells. These findings provide insight into the potential molecular mechanisms by which air pollution may contribute to breast cancer development and highlight CCNE2 as a possible biomarker for prognosis and environmental risk assessment.