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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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  • 2018

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...

Alhamdow, A.; Lindh, C.; Hagberg, J.; Graff, Pål; Westberg, H.; Krais, A.M.; Albin, M.; Gustavsson, P.; Tinnerberg, H.; Broberg, K.
Carcinogenesis 39(7): 869–878
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