Occupational exposure to polycyclic aromatic hydrocarbons and early biomarkers related to cardiovascular disease and cancer

Polycyclic aromatic hydrocarbons (PAH) are omnipresent environmental pollutants composed of fused benzene rings and mainly produced by incomplete combustion of organic material. PAH exposure has been associated with increased risk of cancer and probably cardiovascular disease (CVD). In one way or another, everyone is exposed to PAH, but the dose and the period of exposure vary between individuals. Workers who remove soot from chimneys (chimney sweeps) are likely exposed to higher levels of PAH compared with the general population. However, whether the current PAH exposure among chimney sweeps leads to disease is not known. The overall aim of this thesis was to evaluate PAH exposure among currently working chimney sweeps as well as explore early biomarkers related to cardiovascular disease (CVD) and cancer. For this purpose, we recruited 151 chimney sweeps and 152 unexposed control individuals, all males from southern Sweden, from whom we collected questionnaires and biological samples. In one of the studies, we additionally used data and biological samples from 19 creosote-exposed workers, i.e. workers who impregnate wood panels with black oily material rich in PAH known as creosote. We found that PAH exposure (measured as PAH metabolites in urine) was up to 7 times higher among chimney sweeps compared with unexposed control workers, and the levels of PAH metabolites were positively associated with diastolic blood pressure. Moreover, we found higher serum concentrations of the classical risk markers for CVD (homocysteine and cholesterol) in chimney sweeps, compared with controls. Further, we found 25 putative CVD-related serum proteins differentially expressed between nonsmoking chimney sweeps and controls, among which follistatin (FS), heat shock protein beta-1 (HSP 27), and pro-interleukin-16 (IL-16) showed positive dose-response relationships with PAH metabolites. Pathway analysis demonstrated that these 25 proteins were mainly involved in inflammatory response and immune function. We also demonstrated hypomethylation (lower methylation) of the genes F2RL3 and AHRR, risk markers for lung cancer, among chimney sweeps and creosote-exposed workers, compared with controls. Notably, creosote-exposed workers had the highest PAH exposure and the lowest DNA methylation, compared with both chimney sweeps and controls, which suggests a dose-response relationship. In addition, we found 17 putative cancer-related serum proteins differentially expressed between nonsmoking chimney sweeps and controls, among which kallikrein-13 (KLK13) showed positive dose-response relationships with the metabolites of carcinogenic PAH (BaP and BaA). Pathway analysis showed that most of the differentially expressed proteins were involved in cell movement, cell migration, and cell invasion. Overall, findings from this thesis indicate that (i) currently working chimney sweeps are markedly exposed to PAH, (ii) chimney sweeps showed molecular changes related to CVD and cancer, and (iii) some of these molecular changes seem to be, at least partly, induced by PAH exposure. These results stress that protective measures are warranted to reduce PAH exposure among chimney sweeps as well as other occupational groups at risk of PAH exposure. In addition, further research exploring mechanisms of PAH-induced CVD and cancer is encouraged in order to develop strategies of early detection of disease among individuals known to be exposed to PAH

Occupational exposure to polycyclic aromatic hydrocarbons and early biomarkers related to cardiovascular disease and cancer [Elektronisk resurs]

Polycyclic aromatic hydrocarbons (PAH) are omnipresent environmental pollutants composed of fused benzene rings and mainly produced by incomplete combustion of organic material. PAH exposure has been associated with increased risk of cancer and probably cardiovascular disease (CVD). In one way or another, everyone is exposed to PAH, but the dose and the period of exposure vary between individuals. Workers who remove soot from chimneys (chimney sweeps) are likely exposed to higher levels of PAH compared with the general population. However, whether the current PAH exposure among chimney sweeps leads to disease is not known. The overall aim of this thesis was to evaluate PAH exposure among currently working chimney sweeps as well as explore early biomarkers related to cardiovascular disease (CVD) and cancer. For this purpose, we recruited 151 chimney sweeps and 152 unexposed control individuals, all males from southern Sweden, from whom we collected questionnaires and biological samples. In one of the studies, we additionally used data and biological samples from 19 creosote-exposed workers, i.e. workers who impregnate wood panels with black oily material rich in PAH known as creosote. We found that PAH exposure (measured as PAH metabolites in urine) was up to 7 times higher among chimney sweeps compared with unexposed control workers, and the levels of PAH metabolites were positively associated with diastolic blood pressure. Moreover, we found higher serum concentrations of the classical risk markers for CVD (homocysteine and cholesterol) in chimney sweeps, compared with controls. Further, we found 25 putative CVD-related serum proteins differentially expressed between nonsmoking chimney sweeps and controls, among which follistatin (FS), heat shock protein beta-1 (HSP 27), and pro-interleukin-16 (IL-16) showed positive dose-response relationships with PAH metabolites. Pathway analysis demonstrated that these 25 proteins were mainly involved in inflammatory response and immune function. We also demonstrated hypomethylation (lower methylation) of the genes F2RL3 and AHRR, risk markers for lung cancer, among chimney sweeps and creosote-exposed workers, compared with controls. Notably, creosote-exposed workers had the highest PAH exposure and the lowest DNA methylation, compared with both chimney sweeps and controls, which suggests a dose-response relationship. In addition, we found 17 putative cancer-related serum proteins differentially expressed between nonsmoking chimney sweeps and controls, among which kallikrein-13 (KLK13) showed positive dose-response relationships with the metabolites of carcinogenic PAH (BaP and BaA). Pathway analysis showed that most of the differentially expressed proteins were involved in cell movement, cell migration, and cell invasion. Overall, findings from this thesis indicate that (i) currently working chimney sweeps are markedly exposed to PAH, (ii) chimney sweeps showed molecular changes related to CVD and cancer, and (iii) some of these molecular changes seem to be, at least partly, induced by PAH exposure. These results stress that protective measures are warranted to reduce PAH exposure among chimney sweeps as well as other occupational groups at risk of PAH exposure. In addition, further research exploring mechanisms of PAH-induced CVD and cancer is encouraged in order to develop strategies of early detection of disease among individuals known to be exposed to PAH

Cancer-related proteins in serum are altered in workers occupationally exposed to polycyclic aromatic hydrocarbons : a cross-sectional study

Exposure to some polycyclic aromatic hydrocarbons (PAH) increases the risk of cancer and is common, particularly for workers in occupations such as chimney sweeping. In exposed workers, screening of early cancer-related markers provides important information to identify individuals at risk. Here, we aimed to elucidate the associations between PAH exposure and serum levels of cancer-related proteins in 118 chimney sweeps and 126 occupationally unexposed controls, all non-smoking males from Sweden. Monoydroxylated metabolites of pyrene, phenanthrene, benzo[a]pyrene, and benzo[a]anthracene were measured in urine using LC/MS/MS and 90 cancer-related proteins were measured in serum using a Proximity Extension Assay. Linear regression analysis adjusted for age, BMI, and false discovery rate (FDR) identified 17 serum proteins that were differentially expressed (16 upregulated and 1 downregulated) in chimney sweeps compared with controls (FDR<0.05). Concentrations of the peptidase kallikrein 13 (KLK13) showed significant positive associations with urinary concentrations of the PAH metabolites 3-hydroxybenzo[a]pyrene (B, 95%CI: 0.042, 0.008-0.076) and 3-hydroxybenzo[a]anthracene (B, 95%CI: 0.068, 0.002-0.134). Moreover, dose-response relationships were observed between KLK13 and 3-hydroxybenzo[a]pyrene (trend test P=0.027) and 3-hydroxybenzo[a]anthracene (P=0.035). Pathway and gene ontology analyses showed that cell movement, cell adhesion, and cell migration were the predominant molecular functions associated with the top differentially expressed proteins. In conclusion, we found a number of putative cancer-related proteins differentially expressed in workers exposed to PAH. This warrants effective measure to reduce PAH exposure among workers as well as further investigation to confirm these findings

Cardiovascular Disease-Related Serum Proteins in Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons

AbstractChimney sweeps have higher incidence and mortality of cardiovascular disease (CVD), likely related to their exposure to polycyclic aromatic hydrocarbons (PAH). In order to identify underlying mechanisms of PAH-related CVD, we here investigated whether PAH exposure was associated with levels of putative CVD-related proteins in serum among currently working chimney sweeps. We enrolled 116 chimney sweeps and 125 unexposed controls, all nonsmoking male workers from Sweden. We measured monohydroxylated PAH metabolites in urine by liquid chromatography coupled to tandem mass spectrometry and a panel of 85 proteins in serum using proximity extension assay. Linear regression analysis adjusted for age and body mass index showed that 25 proteins were differentially expressed between chimney sweeps and the controls (p &lt; .05, adjusted for false discovery rate). Of the 25 proteins, follistatin (FS), prointerleukin-16 (IL-16), and heat shock protein beta-1 (HSP 27) showed positive associations with the monohydroxylated metabolites of PAH in a dose-response manner (p &lt; .05). Pathway and gene ontology analyses demonstrated that the differentially expressed proteins were mainly involved in inflammatory response and immunological functions, such as leukocyte migration, cell movement of leukocytes, and adhesion of immune cells. In conclusion, we found a number of putative CVD-related proteins differentially expressed, between PAH-exposed and unexposed individuals, and mainly involved in inflammation and immune function. Our data warrant protective measures to reduce PAH exposure and longitudinal investigations of the protein profile in chimney sweeps and other occupational groups exposed to PAH.</jats:p

Chimney sweeps in Sweden : a questionnaire-based assessment of long-term changes in work conditions, and current eye and airway symptoms

Objectives: To explore chimney sweeping work tasks, chimney sweeps’ use of protective equipment, and type of fuel used by clients, over time. Further, to assess work-relatedness of current eye and airway symptoms. Methods: In a cross-sectional study in 2011, male Swedish chimney sweeps (n = 483; age 21–69 years) answered a questionnaire about their occupational history and eye and airway symptoms. Results: Between 1960 and 2010, black-soot-sweeping in private homes was the major task, although it decreased during the time period, for chimney sweeps. Between 1975 and 2010, the use of petroleum oil decreased, whereas the use of pellets and wood increased. Also, the use of gloves and masks increased significantly. Black-soot-sweeping in industry was associated with work-related eye symptoms (prevalence odds ratio POR = 3.76, 95% CI: 1.72–8.24, for every 10% increment of working time, adjusted for age and tobacco smoking). Chimney sweeps also had slightly higher prevalence of cough with increasing black-soot-sweeping (POR = 1.06, 95% CI: 0.99–1.13 for every 10% increment, further adjusted for the use of mask), and the association was more pronounced, although nonsignificant, for black-soot-sweeping in industry (adjusted POR = 1.26, 95% CI: 0.98–1.61). Conclusions: Chimney sweeping tasks and use of protective equipment as well as type of fuel used by the clients changed significantly over the last 35 years, which may have changed chimney sweeps’ exposure to soot. Still, chimney sweeps in Sweden have black-soot-sweeping-related eye and airway symptoms

Early markers of cardiovascular disease are associated with occupational exposure to polycyclic aromatic hydrocarbons

Occupational exposure to soot, rich in polycyclic aromatic hydrocarbons (PAH), has been associated with increased risk of cardiovascular disease (CVD). However, our knowledge about PAH exposure and early markers of CVD remains limited. In this cross-sectional study of 151 chimney sweeps and 152 controls, we investigated occupational exposure to PAH and early markers of CVD. Blood pressure (BP) (chimney sweeps only), urinary PAH metabolites and serum biomarkers were measured (C-reactive protein, homocysteine, gamma-glutamyltransferase, cholesterol, HDL, LDL, and triglycerides). Chimney sweeps had up to 7 times higher concentrations of PAH metabolites in urine than controls (P < 0.001): Median concentrations (adjusted for specific gravity) for 1-hydroxypyrene, 2-hydroxyphenanthrene, 3-hydroxybenzo[a]pyrene, and 3-hydroxybenzo[a]anthracene were 0.56 μg/L, 0.78 μg/L, 4.75 ng/L, and 6.28 ng/L, respectively. Compared with controls, chimney sweeps had increased homocysteine, cholesterol, and HDL (β = 3.4 μmol/L, 0.43 mmol/L, and 0.13 mmol/L, respectively, P ≤ 0.003, adjusted for age, BMI, and smoking). In chimney sweeps, PAH metabolites correlated positively with the percentage of soot sweeping (P < 0.001). 2-hydroxyphenanthrene, 3-hydroxybenzo[a]pyrene, and 3-hydroxybenzo[a]anthracene were positively associated with diastolic BP (P < 0.044, adjusted for age, BMI, and smoking). PAH exposure among chimney sweeps resulted in elevated levels of markers for CVD risk. These findings stress the need to reduce occupational exposure to PAH

Cardiovascular Disease-Related Serum Proteins in Workers Occupationally Exposed to Polycyclic Aromatic Hydrocarbons

Chimney sweeps have higher incidence and mortality of cardiovascular disease (CVD), likely related to their exposure to polycyclic aromatic hydrocarbons (PAH). In order to identify underlying mechanisms of PAH-related CVD, we here investigated whether PAH exposure was associated with levels of putative CVD-related proteins in serum among currently working chimney sweeps. We enrolled 116 chimney sweeps and 125 unexposed controls, all nonsmoking male workers from Sweden. We measured monohydroxylated PAH metabolites in urine by liquid chromatography coupled to tandem mass spectrometry and a panel of 85 proteins in serum using proximity extension assay. Linear regression analysis adjusted for age and body mass index showed that 25 proteins were differentially expressed between chimney sweeps and the controls (p <. 05, adjusted for false discovery rate). Of the 25 proteins, follistatin (FS), prointerleukin-16 (IL-16), and heat shock protein beta-1 (HSP 27) showed positive associations with the monohydroxylated metabolites of PAH in a dose-response manner (p <. 05). Pathway and gene ontology analyses demonstrated that the differentially expressed proteins were mainly involved in inflammatory response and immunological functions, such as leukocyte migration, cell movement of leukocytes, and adhesion of immune cells. In conclusion, we found a number of putative CVD-related proteins differentially expressed, between PAH-exposed and unexposed individuals, and mainly involved in inflammation and immune function. Our data warrant protective measures to reduce PAH exposure and longitudinal investigations of the protein profile in chimney sweeps and other occupational groups exposed to PAH