Back

Clonal hematopoiesis associated non-small cell lung cancer risk is potentiated by small particulate matter air pollution

Vlasschaert, C.; Buttigieg, M.; Pershad, Y.; Lanktree, M. B.; Aldrich, M. C.; Rauh, M. J.; Bick, A. G.

2024-01-17 genetic and genomic medicine
10.1101/2024.01.17.24301439 medRxiv
Show abstract

Small particulate matter air pollution (PM2.5) is a recognized driver of non-small cell lung cancer (NSCLC) among 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. We sought to determine whether clonal hematopoiesis of indeterminate potential (CHIP), a common age-related condition characterized by hyperinflammatory macrophages, exacerbates PM2.5-associated NSCLC in non-smokers using genetic, environmental, and phenotypic data from 413,901 individuals in the UK Biobank. Among non-smokers, PM2.5 is not associated with NSCLC and not associated with prevalence of CHIP, but CHIP is associated with a doubling of NSCLC risk (hazard ratio (HR) 2.01, 95% confidence interval (CI): 1.34-3.00). Moreover, CHIP-associated NSCLC risk is exacerbated in the setting of above-median PM2.5 levels (HR 2.70, 95% CI: 1.60-4.55). PM2.5 x CHIP is also associated with significantly greater markers of systemic inflammation (CRP, IL-6, and IL-1{beta}) than expected. Altogether, these results suggest CHIP and PM2.5 form a novel gene x environment interaction promoting NSCLC tumorigenesis in non-smokers.

Matching journals

The top 9 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.