Margaret Quaid, Jaclyn M. Goodrich, Miriam M. Calkins, Judith M. Graber, Derek Urwin, Jamie Gabriel, Alberto J. Caban-Martinez, Rebekah L. Petroff, Casey Grant, Shawn C. Beitel, Sally Littau, John J. Gulotta, Darin Wallentine, Jeff Hughes, Jefferey L. Burgess
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引用次数: 0
摘要
前列腺癌是美国男性发病率最高的癌症。消防员被诊断患有这种疾病的比例是普通人群的 1.21 倍。这种风险的增加可能是由于职业暴露于许多有毒物质,包括全氟和多氟烷基物质 (PFAS)。本研究评估了一般消防职业或 PFAS 血清水平与 DNA 甲基化之间的关系。研究只选择了以前与前列腺癌风险有关的基因组区域进行分析:GSTP1、Alu重复元件和8q24染色体区域。这项研究共纳入了 444 名男性消防员,其中一些分析是在人数较少的情况下进行的,原因是存在遗漏。研究采用统计模型来检验暴露与所选基因组区域 CpG 位点 DNA 甲基化之间的关联。暴露变量包括累积消防暴露的替代物(在职与在校状态以及消防经验年数)和暴露于 PFAS 的生物标志物(9 种 PFAS 的血清浓度)。累积暴露的代用指标与 15 个 CpG 位点和位于 FAM83A 中的一个区域的 DNA 甲基化相关(q-value
Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk
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.
期刊介绍:
Environmental and Molecular Mutagenesis publishes original research manuscripts, reviews and commentaries on topics related to six general areas, with an emphasis on subject matter most suited for the readership of EMM as outlined below. The journal is intended for investigators in fields such as molecular biology, biochemistry, microbiology, genetics and epigenetics, genomics and epigenomics, cancer research, neurobiology, heritable mutation, radiation biology, toxicology, and molecular & environmental epidemiology.