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Original research
Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
  1. Ayman Alhamdow1,
  2. Yona J Essig2,
  3. Annette M Krais2,
  4. Per Gustavsson1,3,
  5. Håkan Tinnerberg4,
  6. Christian H Lindh2,
  7. Jessika Hagberg5,6,
  8. Pål Graff7,
  9. Maria Albin1,2,3,
  10. Karin Broberg1,2
  1. 1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  2. 2 Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
  3. 3 Region Stockholm, Centre for Occupational and Environmental Medicine, Stockholm, Sweden
  4. 4 School of Public Health and Community Medicine, Section of Occupational and Environmental Medicine, University of Gothenburg Sahlgrenska Academy, Göteborg, Sweden
  5. 5 MTM Research Centre, Örebro universitet Akademin för Naturvetenskap och Teknik, Orebro, Sweden
  6. 6 Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
  7. 7 Department of Chemical and Biological Work Environment, STAMI, Oslo, Norway
  1. Correspondence to Dr Karin Broberg, Institute of Environmental Medicine, Karolinska Institutet, Stockholm SE-171 76, Sweden; karin.broberg{at}


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 of F2RL3 and AHRR using 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). ∑OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation of F2RL3 and AHRR in chimney sweeps (B (95% CI)=–2.7 (–3.9 to –1.5) for F2RL3_cg03636183, and –7.1 (–9.6 to –4.7) for AHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, ∑OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation of AHRR CpG2.

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 of F2RL3 and AHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.

  • smoking
  • health care workers
  • risk assessment
  • cross sectional studies
  • cancer

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  • AA and YJE contributed equally.

  • Contributors AA: drafted the manuscript and performed the statistical analysis. YJE: drafted the manuscript and performed the PAH metabolites analysis. AMK and CHL: planned and optimised the PAH metabolites analysis. PG and MA: interpreted the study findings. HT: recruited chimney sweeps and creosote-exposed workers and carried out the occupational hygienic assessment. JH and PG: recruited creosote-exposed workers. KB: designed the study, recruited the chimney sweeps and controls, and interpreted the data. All authors critically reviewed the manuscript and agreed with the final version.

  • Funding This study was financially supported by the Swedish Research Council for Health, Working Life and Welfare (FORTE) (grant#: 2012-00402), the Medical Training and Research Agreement (ALF grants; Region Örebro län) (grant#: OLL-550721), AFA Insurance (AFA Försäkring) (grant#: 120115) and Karolinska Institutet. YJE was supported by a fellowship from the German Research Foundation (DFG).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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