| Title: | Air pollution modifies clonal hematopoiesis-associated non-small cell lung cancer risk in non-smoking individuals |
| Journal: | Journal of the National Cancer Institute |
| Published: | 27 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42202166/ |
| DOI: | https://doi.org/10.1093/jnci/djag159 |
Publication 19902
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Abstract
Small particulate matter air pollution (PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC), including in non-smoking individuals. Inhaled PM2.5 recruits pro-inflammatory macrophages to the air-lung interface, which promotes malignant lung epithelial cell growth and progression to overt cancer. Smoking is recognized to potentiate this process, though no factors potentiating risk among non-smoking individuals have been identified. We sought to determine whether clonal hematopoiesis of indeterminate potential (CHIP), a common age-related condition characterized by hyperinflammatory macrophages, synergizes with PM2.5 to promote NSCLC in non-smoking individuals using genetic, environmental, and phenotypic data from over 650,000 people in the UK Biobank and All of Us cohorts. In meta-analysis, CHIP was associated with a greater risk of NSCLC in never-smoking participants (hazard ratio (HR)=1.76[1.07-2.89]). This risk is exacerbated in the setting of above-median PM2.5 levels (HR = 2.51[1.55 to 4.05]; p-interaction = 0.02). The CHIP x PM2.5 interaction also associated with elevated markers of systemic inflammation (CRP, IL-6, and IL-1β). Together, these results suggest CHIP and PM2.5 form a novel somatic gene × environment interaction promoting inflammation and NSCLC tumorigenesis in non-smoking individuals.</p>
7 Authors
- Marco M Buttigieg
- Caitlyn Vlasschaert
- Yash Pershad
- Matthew Lanktree
- Melinda C Aldrich
- Michael J Rauh
- Alexander G Bick
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