Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Carcinogenesis. 2019 Jul 6;40(6):771-781. doi: 10.1093/carcin/bgz022.
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.
多环芳烃(PAH)暴露会增加癌症风险,在烟囱清洁工等特定职业的工人中尤为常见。在暴露于多环芳烃的工人中,早期癌症相关标志物的筛查可提供重要信息,以识别处于风险中的个体。在这里,我们旨在阐明 118 名烟囱清洁工和 126 名职业未暴露对照者(均来自瑞典的不吸烟男性)中 PAH 暴露与血清中癌症相关蛋白水平之间的关联。使用液相色谱串联质谱法检测尿液中苊、芘、苯并[a]芘和苯并[a]蒽的单羟基代谢物,并使用邻近延伸分析检测血清中的 90 种癌症相关蛋白。线性回归分析调整了年龄和体重指数,以及错误发现率(FDR)鉴定出 17 种血清蛋白在烟囱清洁工中与对照者相比差异表达(16 种上调和 1 种下调)(FDR<0.05)。肽酶激肽释放酶 13(KLK13)的浓度与尿液中 PAH 代谢物 3-羟基苯并[a]芘(3-OH-BaP)[B,95%置信区间(CI):0.042,0.008-0.076]和 3-羟基苯并[a]蒽(3-OH-BaA)(B,95%CI:0.068,0.002-0.134)的浓度呈显著正相关。此外,在 KLK13 与 3-OH-BaP(趋势检验 P=0.027)和 3-OH-BaA(P=0.035)之间观察到剂量反应关系。途径和基因本体分析表明,细胞运动、细胞黏附和细胞迁移是与差异表达蛋白相关的主要分子功能。总之,我们发现了一些在接触多环芳烃的工人中差异表达的潜在癌症相关蛋白。这需要采取有效措施来减少工人中多环芳烃的暴露,并进一步调查以证实这些发现。