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| Item Type: | Article |
|---|---|
| Title: | Smoking-associated gene expression alterations in nasal epithelium reveal immune impairment linked to lung cancer risk |
| Creators Name: | de Biase, M.S. and Massip, F. and Wei, T.T. and Giorgi, F.M. and Stark, R. and Stone, A. and Gladwell, A. and O'Reilly, M. and Schütte, D. and de Santiago, I. and Meyer, K.B. and Markowetz, F. and Ponder, B.A.J. and Rintoul, R.C. and Schwarz, R.F. |
| Abstract: | BACKGROUND: Lung cancer is the leading cause of cancer-related death in the world. In contrast to many other cancers, a direct connection to modifiable lifestyle risk in the form of tobacco smoke has long been established. More than 50% of all smoking-related lung cancers occur in former smokers, 40% of which occur more than 15 years after smoking cessation. Despite extensive research, the molecular processes for persistent lung cancer risk remain unclear. We thus set out to examine whether risk stratification in the clinic and in the general population can be improved upon by the addition of genetic data and to explore the mechanisms of the persisting risk in former smokers. METHODS: We analysed transcriptomic data from accessible airway tissues of 487 subjects, including healthy volunteers and clinic patients of different smoking statuses. We developed a computational model to assess smoking-associated gene expression changes and their reversibility after smoking is stopped, comparing healthy subjects to clinic patients with and without lung cancer. RESULTS: We find persistent smoking-associated immune alterations to be a hallmark of the clinic patients. Integrating previous GWAS data using a transcriptional network approach, we demonstrate that the same immune- and interferon-related pathways are strongly enriched for genes linked to known genetic risk factors, demonstrating a causal relationship between immune alteration and lung cancer risk. Finally, we used accessible airway transcriptomic data to derive a non-invasive lung cancer risk classifier. CONCLUSIONS: Our results provide initial evidence for germline-mediated personalized smoke injury response and risk in the general population, with potential implications for managing long-term lung cancer incidence and mortality. |
| Keywords: | Lung, Lung Neoplasms, Nasal Mucosa, Nicotiana, Smoking, Transcriptome |
| Source: | Genome Medicine |
| ISSN: | 1756-994X |
| Publisher: | BioMed Central |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 54 |
| Date: | 8 April 2024 |
| Official Publication: | https://doi.org/10.1186/s13073-024-01317-4 |
| PubMed: | View item in PubMed |
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