A systematic review of observational studies on long-term air pollution exposure and epigenetic alterations in adults

Background Evidence suggests that environmental exposures induce epigenetic modifications that can have long-lasting effects on multiple health outcomes, and an in-depth review of the epidemiological evidence is urgent. We aimed to comprehensively assess the associations between long-term exposure to air pollution and epigenetic changes in adults. Methods We systematically searched EMBASE, MEDLINE, and Web of Science databases for relevant articles published in English from inception through 17 November 2023. We assessed and narratively synthesised eligible studies on ambient (i.e. non-occupational) and epigenetic alterations in adults. We separately documented relevant occupational studies identified by the search. Results We analysed 52 eligible articles, including 30 ambient air pollution and 22 occupational air pollution exposure studies. Long-term exposure to ambient particulate matter (PM) with aerodynamic diameters of ≤2.5 μm (PM2.5) and ≤10 μm, (PM10), and nitrogen oxides (NOx) showed no consistent association with global DNA methylation across different studies in adults. Two candidate-gene studies indicated that sex-determining region Y-box 2 (SOX2) hypermethylation was associated with ambient PM2.5 exposure. Results from epigenome-wide association studies suggest that long-term exposure to specific ambient air pollutants can alter blood methylation at up to 189 loci. In addition, decreased methylation of cg00475490 by polychlorinated biphenyls, increased methylation in cg08500171 associated with nitrogen dioxide (NO2) exposure, and decreased methylation in cg17629796 associated with PM2.5 exposure were successfully replicated in external validation cohorts. Epigenetic alterations in specific genes were associated with multiple occupational exposures. Conclusions We demonstrated that long-term exposure to air pollution is associated with locus-specific methylation changes and histone modification in adults. Further elucidation of these epigenetic changes through epidemiological and laboratory work could provide new avenues to identify potential biomarkers linked to air pollutant exposure and to clarify their impacts on health outcomes. Registration PROSPERO: CRD42023480771.