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DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. (MTM Research Centre)ORCID iD: 0000-0003-4128-8226
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; National Institute of Occupational Health, Oslo, Norway.ORCID iD: 0000-0003-4928-617X
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2018 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 39, no 7, p. 869-878Article in journal (Refereed) Published
Abstract [en]

Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1% and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B=-2.04; P<0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P<0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P<0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.

Place, publisher, year, edition, pages
Oxford University Press, 2018. Vol. 39, no 7, p. 869-878
National Category
Occupational Health and Environmental Health Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-67021DOI: 10.1093/carcin/bgy059ISI: 000438289600003PubMedID: 29722794OAI: oai:DiVA.org:oru-67021DiVA, id: diva2:1213298
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2012-00402AFA Insurance, 120115The Karolinska Institutet's Research Foundation
Note

Funding Agency:

Medical Training and Research Agreement (ALF grants; Region Örebro län)  OLL-550721

Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-09-11Bibliographically approved

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Hagberg, JessikaGraff, PålWestberg, Håkan

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