Metabolomics Signatures of Exposure to Ambient Air Pollution: A Large-Scale Metabolome-Wide Association Study in the Cancer Prevention Study-II Nutrition Cohort

Existing air pollution metabolomics studies showed inconsistent
results, often limited by small sample size and individual air pollutants
effects. We conducted a metabolome-wide association study among 1096
women (68.2 ± 5.7 years) who provided blood samples (1998–2001)
within the Cancer Prevention Study-II Nutrition Cohort. Annual average
individual exposures to particulate matter, nitrogen dioxide, ozone,
sulfur dioxide, and carbon monoxide in the year of blood draw were
used. Metabolomics profiling was conducted on serum samples by Metabolon.
We evaluated the individual air pollutants effects using multiple
linear regression and the mixture effect using quantile g-computation,
adjusting for confounders and false discovery rate (FDR). Ninety-five
metabolites were significantly associated with at least one air pollutant
or mixture (FDR < 0.05). These metabolites were enriched in pathways
related to oxidative stress, systemic inflammation, energy metabolism,
signals transduction, nucleic acid damage and repair, and xenobiotics.
Sixty metabolites were confirmed with level 1 or 2 evidence, among
which 21 have been previously linked to air pollution exposure, including
taurine, creatinine, and sebacate. Overall, our results replicate
prior findings in a large sample and provide novel insights into biological
responses to long-term air pollution exposure using mixture analysis.