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DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons

Alhamdow, Ayman LU ; Lindh, Christian LU orcid ; Hagberg, Jessika ; Graff, Pål ; Westberg, Håkan ; Krais, Annette M LU orcid ; Albin, Maria LU ; Gustavsson, Per ; Tinnerberg, Håkan LU and Broberg, Karin LU orcid (2018) In Carcinogenesis 39(7). p.869-878
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Carcinogenesis
volume
39
issue
7
pages
869 - 878
publisher
Oxford University Press
external identifiers
  • pmid:29722794
  • scopus:85048477535
ISSN
0143-3334
DOI
10.1093/carcin/bgy059
language
English
LU publication?
yes
id
a6d9bd1a-d0d8-4d4e-976f-64bb8f9b1292
date added to LUP
2018-06-14 18:21:15
date last changed
2025-10-15 22:28:32
@article{a6d9bd1a-d0d8-4d4e-976f-64bb8f9b1292,
  abstract     = {{<p>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&lt;0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P&lt;0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P&lt;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.</p>}},
  author       = {{Alhamdow, Ayman and Lindh, Christian and Hagberg, Jessika and Graff, Pål and Westberg, Håkan and Krais, Annette M and Albin, Maria and Gustavsson, Per and Tinnerberg, Håkan and Broberg, Karin}},
  issn         = {{0143-3334}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{869--878}},
  publisher    = {{Oxford University Press}},
  series       = {{Carcinogenesis}},
  title        = {{DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons}},
  url          = {{http://dx.doi.org/10.1093/carcin/bgy059}},
  doi          = {{10.1093/carcin/bgy059}},
  volume       = {{39}},
  year         = {{2018}},
}