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We conducted a metabolome-wide association study among 1096 women (68.2 \u00b1 5.7 years) who provided blood samples (1998\u20132001) 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 &amp;lt; 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.<\/jats:p>","DOI":"10.1021\/acs.est.4c09592","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T11:08:32Z","timestamp":1734347312000},"page":"212-223","source":"Crossref","is-referenced-by-count":22,"title":["Metabolomics Signatures\nof Exposure to Ambient Air\nPollution: A Large-Scale Metabolome-Wide\nAssociation Study in the Cancer Prevention Study-II Nutrition Cohort"],"prefix":"10.1021","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7311-2298","authenticated-orcid":true,"given":"Donghai","family":"Liang","sequence":"first","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyin","family":"Tang","sequence":"additional","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-9000","authenticated-orcid":true,"given":"W. Ryan","family":"Diver","sequence":"additional","affiliation":[{"name":"American Cancer Society , , 270 Peachtree Street NW, Suite 1300 , , ,","place":["Atlanta, Georgia, United States, 30303"]},{"name":"Barcelona Institute for Global Health (ISGlobal) , ,","place":["Barcelona, Spain, 08036"]},{"name":"Universitat Pompeu Fabra (UPF) , ,","place":["Barcelona, Spain, 08018"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Sarnat","sequence":"additional","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-4552","authenticated-orcid":true,"given":"Sabrina S.","family":"Chow","sequence":"additional","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Cheng","sequence":"additional","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Deubler","sequence":"additional","affiliation":[{"name":"American Cancer Society , , 270 Peachtree Street NW, Suite 1300 , , ,","place":["Atlanta, Georgia, United States, 30303"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youran","family":"Tan","sequence":"additional","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-3291","authenticated-orcid":true,"given":"Stephanie M.","family":"Eick","sequence":"additional","affiliation":[{"name":"Emory University , , 1518 Clifton Road , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Jerrett","sequence":"additional","affiliation":[{"name":"University of California Los Angeles , , , ,","place":["Los Angeles, California, United States, 90095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C.","family":"Turner","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal) , ,","place":["Barcelona, Spain, 08036"]},{"name":"Universitat Pompeu Fabra (UPF) , ,","place":["Barcelona, Spain, 08018"]},{"name":"CIBER Epidemiologi\u0301a y Salud Pu\u0301blica (CIBERESP) , ,","place":["Madrid, Spain, 28029"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"American Cancer Society , , 270 Peachtree Street NW, Suite 1300 , , ,","place":["Atlanta, Georgia, United States, 30303"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"2026081212030246400_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2022.107262","article-title":"Long-term exposure to traffic-related\nair pollution and selected health outcomes: A systematic review and\nmeta-analysis","volume":"164","author":"Boogaard","year":"2022","journal-title":"Environ. 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Clin."},{"key":"2026081212030246400_cit4","unstructured":"Integrated Science Assessment (ISA) for Particulate\nMatter, EPA\/600\/R-19\/188\n          U.S. Environment\nProtection Agency: Washington, DC."},{"key":"2026081212030246400_cit5","unstructured":"Integrated Science Assessment (ISA) for Ozone and\nRelated Photochemical\nOxidants, EPA\/600\/R-20\/012\n          U.S. Environment\nProtection Agency: Washington, DC."},{"issue":"8","key":"2026081212030246400_cit6","doi-asserted-by":"publisher","DOI":"10.1289\/EHP1249","article-title":"Ambient\nair pollution and cancer mortality in the cancer prevention study\nII","volume":"125","author":"Turner","year":"2017","journal-title":"Environ. 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Breath\nRes."},{"issue":"9","key":"2026081212030246400_cit21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0203468","article-title":"Particulate\nmetal exposures induce plasma metabolome changes in a commuter panel\nstudy","volume":"13","author":"Ladva","year":"2018","journal-title":"PLoS One"},{"key":"2026081212030246400_cit22","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.envint.2019.04.003","article-title":"Perturbations of\nthe arginine metabolome following exposures to traffic-related air\npollution in a panel of commuters with and without asthma","volume":"127","author":"Liang","year":"2019","journal-title":"Environ. 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Health\nPerspect."},{"key":"2026081212030246400_cit47","doi-asserted-by":"publisher","DOI":"10.1289\/isee.2020.virtual.P-0002","article-title":"Systematic Review on\nUntargeted Metabolomics Application\nin Air Pollution Health Research: Current Progress, Analytical Challenges,\nand Future Direction","volume":"2020","author":"Liang","year":"2020","journal-title":"ISEE Conf. Abstr."},{"key":"2026081212030246400_cit48","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.159014","article-title":"Joint effect\nof multiple air pollutants on cardiometabolic health in normal-weight\nand obese adults: A novel insight into the role of circulating free\nfatty acids","volume":"856","author":"Zhang","year":"2023","journal-title":"Sci. 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