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

Journal article
Authors Ayman Alhamdow
Christian Lindh
Jessika Hagberg
Pål Graff
Håkan Westberg
Annette M Krais
Maria Albin
Per Gustavsson
Håkan Tinnerberg
Karin Broberg
Published in Carcinogenesis
Volume 39
Issue 7
Pages 869-878
ISSN 1460-2180
Publication year 2018
Published at
Pages 869-878
Language en
Links dx.doi.org/10.1093/carcin/bgy059
www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adult, Aged, Basic Helix-Loop-Helix Transcription Factors, genetics, Biomarkers, Tumor, genetics, Carcinogens, toxicity, Creosote, adverse effects, DNA Methylation, drug effects, DNA, Mitochondrial, genetics, Humans, Lung Neoplasms, chemically induced, genetics, Male, Middle Aged, Occupational Exposure, adverse effects, Polycyclic Aromatic Hydrocarbons, adverse effects, Receptors, Thrombin, genetics, Repressor Proteins, genetics, Sweden, Young Adult
Subject categories Environmental Health and Occupational Health

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 (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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