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

Abstract

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 liquid chromatography coupled to tandem mass spectrometry and 90 cancer-related proteins were measured in serum using a proximity extension assay. Linear regression analysis adjusted for age and body mass index, 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 (3-OH-BaP) [B, 95% confidence interval (CI): 0.042, 0.008-0.076] and 3-hydroxybenzo[a]anthracene (3-OH-BaA) (B, 95% CI: 0.068, 0.002-0.134). Moreover, dose-response relationships were observed between KLK13 and 3-OH-BaP (trend test P = 0.027) and 3-OH-BaA (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.

Figure 1.

Correlations between concentrations of PAH metabolites in urine and serum proteins. (a) Heatmap of Spearman’s correlations between the top 17 differentially expressed proteins and PAH metabolite concentrations in urine for chimney sweeps, controls and for both chimney sweeps and controls together. The order of the proteins was set according to the Spearman’s rho of 1-OH-PYR versus protein concentrations (for all participants together) in a descending fashion (left-most column). NPX values (log₂-transformed) for serum proteins were used. 1-OH-PYR and 2-OH-PH concentrations were μg/g creatinine, whereas 3-OH-BaP and 3-OH-BaA concentrations were ng/g creatinine. (b) Serum concentrations of KLK13 across quartiles of 3-OH-BaP and 3-OH-BaA among chimney sweeps. *P-value of Jonckheere–Terpstra trend test to examine the hypothesis that KLK13 concentrations in serum are increasing across the quartiles of 3-OH-BaP and 3-OH-BaA.