PDF(Pubmed)
Abstract：
Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per- and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q-value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically.
摘要：
前列腺癌是美国男性中最常见的癌症。消防员被诊断出患有这种疾病的比率是平均人口的1.21倍。这种增加的风险可能是由于职业暴露于许多有毒物质，包括全氟烷基和多氟烷基物质(PFAS)。这项研究评估了消防作为一般职业或PFAS血清水平之间的关联，DNA甲基化。仅选择先前与前列腺癌风险相关的基因组区域进行分析：GSTP1，Alu重复元件，和8q24染色体区域。这项研究包括444名男性消防员，一些分析是在较少的参与者上进行的，因为这是不恰当的。使用统计模型来测试暴露与所选基因组区域中CpG位点处的DNA甲基化之间的关联。暴露变量包括累积消防暴露的代理（现任与学术地位和多年的消防经验）和PFAS暴露的生物标志物（9PFAS的血清浓度）。累积暴露的代理与15个CpG位点和位于FAM83A内的一个区域的DNA甲基化相关(q值<0.1)。SbPFOA与19个CpG位点（q<0.1）相关，但由于检出率低,这种PFAS被建模为在血清中检测到和未检测到.总的来说,有证据表明，消防经验与前列腺癌风险位点的差异DNA甲基化有关，但这项研究没有发现证据表明这些差异是由于PFAS暴露所致.
