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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 ; Hagberg, Jessika; Graff, Pål; Westberg, Håkan; Krais, Annette M LU ; Albin, Maria LU ; Gustavsson, Per; Tinnerberg, Håkan LU and Broberg, Karin LU (2018) In Carcinogenesis p.1-10
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
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Carcinogenesis
pages
1 - 10
publisher
Oxford University Press
external identifiers
  • 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
2018-09-14 03:00:16
@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        = {05},
  pages        = {1--10},
  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},
  year         = {2018},
}