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Therefore, we proposed to evaluate the relationship between PAH exposure, vitamin D, and the risks for 14 cancer types via a causal inference framework underlying the mediation analysis. We evaluated seven urine monohydroxylated PAH (OH\u2010PAH) and serum vitamin D concentrations of 3306 participants from the National Health and Nutrition Examination Survey between the 2013 and 2016 survey cycles and measured PAH concentrations in 150 subjects from the Nanjing cohort. We observed a significant negative dose\u2013response relationship between increased OH\u2010PAH levels and vitamin D deficiency. Each unit increase in \u2211OH\u2010PAHs could lead to a decrease in vitamin D levels (<jats:italic>\u03b2<\/jats:italic><jats:sub>adj<\/jats:sub>\u2009=\u2009\u22120.98, <jats:italic>P<\/jats:italic><jats:sub>adj<\/jats:sub>\u2009=\u20092.05\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Body mass index could have interaction effects with \u2211OH\u2010PAHs and affect vitamin D levels. Coexposure to naphthalene and fluorene metabolites mutually affected vitamin D levels. Notably, vitamin D could causally mediate the relationship between OH\u2010PAHs and nine types of cancer (e.g., colorectal cancer, liver cancers, etc.). This study first emphasizes the causal cascade of individual OH\u2010PAHs, vitamin D, and cancer risk, providing insights into prevention via the environment.<\/jats:p>","DOI":"10.1002\/tox.23835","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T16:29:38Z","timestamp":1684600178000},"page":"2111-2120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of polycyclic aromatic hydrocarbons on cancer risk causally mediated via vitamin D levels"],"prefix":"10.1002","volume":"38","author":[{"given":"Silu","family":"Chen","sequence":"first","affiliation":[{"name":"Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research The Affiliated Cancer Hospital of Nanjing Medical University  Nanjing China"},{"name":"Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Center for Global Health, School of Public Health Nanjing Medical University  Nanjing 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