Air pollution modifies clonal hematopoiesis-associated non-small cell lung cancer risk in non-smoking individuals
Menée à partir de données génétiques, environnementales et phénotypiques de la "UK Biobank" et de "All of Us" portant au total sur plus de 650 000 personnes, cette étude analyse l'interaction des polluants atmosphériques PM2.5 avec l'hématopoïèse clonale de potentiel indéterminé puis évalue l'effet de cette interaction sur le risque de cancer du poumon non à petites cellules chez les non-fumeurs
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.
Journal of the National Cancer Institute , article en libre accès, 2026