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Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Region Stockholm, Centre for Occupational and Environmental Medicine, Stockholm, Sweden.
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2020 (English)In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 77, no 7, p. 488-495Article in journal (Refereed) Published
Abstract [en]

Objectives: Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers.

Methods: We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing.

Results: Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2.

Conclusions: Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2020. Vol. 77, no 7, p. 488-495
Keywords [en]
Cancer, cross sectional studies, health care workers, risk assessment, smoking
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-81768DOI: 10.1136/oemed-2020-106413ISI: 000542728000010PubMedID: 32385190Scopus ID: 2-s2.0-85086524368OAI: oai:DiVA.org:oru-81768DiVA, id: diva2:1429680
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-00402AFA Insurance, 120115The Karolinska Institutet's Research Foundation
Note

Funding Agencies:

Medical Training and Research Agreement (ALF grants; Region Örebro län)  OLL550721

German Research Foundation (DFG)

Available from: 2020-05-12 Created: 2020-05-12 Last updated: 2020-08-12Bibliographically approved

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Hagberg, Jessika

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