Exposure to ambient air pollution and global DNA methylation

Michelle PLUSQUIN, Imperial college London, United Kingdom
GUIDA F. 1 , POLIDORO S. 3 , CAMPANELLA G. 1 , HOEK G. 2 , VERMEULEN R. 2 , CHADEAU-HYAM M. 1 , VINEIS P. 1,3

1 MRC/PHE Centre for Environment and Health, Imperial College London, UK
2 Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
3 HuGeF, Human Genetics Foundation, Torino, Italy

Outdoor air pollution is a complex mixture of particulate matter and gases. It has been associated with several adverse health effects and is carcinogenic to humans. Recent evidence suggests that exposure to air pollution induces changes in DNA methylation, but functional regions of the genome have not been studied yet.
We used data from 2 case-control studies nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. For each of the participants (N=457 from Italy; N=167 from the Netherlands), genome-wide methylation profiles were acquired from blood samples collected at enrolment using the Illumina-HM450 DNA methylation array. Long-term air pollution exposure estimates were calculated using exposure models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The association of DNA methylation per region with ambient air pollution was assessed using beta-regression controlling for technical and confounding factors.
Exposure to NO2 and NOx was associated with significant global hypomethylation on the CpG island’s shores in Italy (β±se = -2.2E-04 ± 6.1E-05, p-value=0.0003, and β±se = -7.3E-05 ± 2.9E-05, p-value=0.0104 for NO2 and NOx, respectively) and in the Netherlands (β±se = -2.3E-03 ± 1.1E-03, p-value=0.0339 and β±se = -1.1E-03 ± 4.7E-04, p-value=0.0188 for NO2 and NOx respectively). Hypomethylation of theCpG island’s shelves was also significantly associated with exposure to NO2 and NOx. The promoter regions were significantly more methylated in association to particles smaller than 10 µm in the Italian dataset.
We observed DNA hypomethylation at CpG island’s shores and shelves with exposure to outdoor NOx and NO2 levels in healthy adults. DNA methylation is involved in genome stability which can be achieved through chromatin structure modelling. A hallmark of cancer is genome instability and as such lower DNA methylation resulting from exposure to NO2 and NOx can enable the development of cancers.