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

## TL;DR

This study reviews how long-term air pollution exposure affects epigenetic changes in adults, finding some specific gene methylation patterns linked to pollutants.

## Contribution

The paper provides a systematic review of observational studies linking long-term air pollution exposure to epigenetic alterations in adults.

## Key findings

- Long-term exposure to PM2.5 and NO2 is associated with methylation changes at specific loci like cg08500171 and cg17629796.
- SOX2 hypermethylation is linked to ambient PM2.5 exposure in candidate-gene studies.
- Epigenome-wide studies show up to 189 methylation loci altered by specific ambient air pollutants.

## Abstract

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.

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.

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.

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.

PROSPERO: CRD42023480771.