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

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  • معلومة اضافية
    • Contributors:
      Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Applied Mass Spectrometry in Environmental Medicine, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för arbets- och miljömedicin, Tillämpad masspektrometri inom miljömedicin, Originator; Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för arbets- och miljömedicin, Originator; Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Environmental health and occupational health, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för arbets- och miljömedicin, Arbetsorganisation och hälsa, Originator; Lund University, Profile areas and other strong research environments, Strategic research areas (SRA), EpiHealth: Epidemiology for Health, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Strategiska forskningsområden (SFO), EpiHealth: Epidemiology for Health, Originator
    • نبذة مختصرة :
      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 notchimney 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.