Department of Population Health, New York University Langone Health, New York, NY 10016, USA.
Foundation Medicine, Cambridge, MA 02141, USA.
Int J Environ Res Public Health. 2022 Apr 22;19(9):5104. doi: 10.3390/ijerph19095104.
Breast cancer represents the most common cancer diagnosis among World Trade Center (WTC)-exposed community members, residents, and cleanup workers enrolled in the WTC Environmental Health Center (WTC EHC). The primary aims of this study were (1) to compare blood DNA methylation profiles of WTC-exposed community members with breast cancer and WTC-unexposed pre-diagnostic breast cancer blood samples, and (2) to compare the DNA methylation differences among the WTC EHC breast cancer cases and WTC-exposed cancer-free controls. Gene pathway enrichment analyses were further conducted. There were significant differences in DNA methylation between WTC-exposed breast cancer cases and unexposed prediagnostic breast cancer cases. The top differentially methylated genes were Intraflagellar Transport 74 (IFT74), WD repeat-containing protein 90 (WDR90), and Oncomodulin (OCM), which are commonly upregulated in tumors. Probes associated with established tumor suppressor genes (ATM, BRCA1, PALB2, and TP53) were hypermethylated among WTC-exposed breast cancer cases compared to the unexposed group. When comparing WTC EHC breast cancer cases vs. cancer-free controls, there appeared to be global hypomethylation among WTC-exposed breast cancer cases compared to exposed controls. Functional pathway analysis revealed enrichment of several gene pathways in WTC-exposed breast cancer cases including endocytosis, proteoglycans in cancer, regulation of actin cytoskeleton, axon guidance, focal adhesion, calcium signaling, cGMP-PKG signaling, mTOR, Hippo, and oxytocin signaling. The results suggest potential epigenetic links between WTC exposure and breast cancer in local community members enrolled in the WTC EHC program.
乳腺癌是世界贸易中心（WTC）暴露人群、居民和 WTC 环境健康中心（WTC EHC）登记的清理工人中最常见的癌症诊断。本研究的主要目的是：(1) 比较 WTC 暴露的社区成员乳腺癌与未暴露的乳腺癌预诊断血样的 DNA 甲基化谱；(2) 比较 WTC EHC 乳腺癌病例与 WTC 暴露的无癌对照的 DNA 甲基化差异。进一步进行了基因途径富集分析。WTC 暴露的乳腺癌病例与未暴露的预诊断乳腺癌病例之间的 DNA 甲基化存在显著差异。差异甲基化的 top 基因是内纤毛运输蛋白 74 (IFT74)、WD 重复蛋白 90 (WDR90)和 Oncomodulin (OCM)，这些基因在肿瘤中通常上调。与未暴露组相比，WTC 暴露的乳腺癌病例中与已确立的肿瘤抑制基因（ATM、BRCA1、PALB2 和 TP53）相关的探针呈高甲基化。与无癌对照相比，WTC EHC 乳腺癌病例似乎表现出 WTC 暴露的乳腺癌病例的整体低甲基化。功能途径分析显示，WTC 暴露的乳腺癌病例中存在几个基因途径的富集，包括内吞作用、癌症中的蛋白聚糖、肌动蛋白细胞骨架调节、轴突导向、焦点黏附、钙信号、cGMP-PKG 信号、mTOR、 Hippo 和催产素信号。结果表明，WTC 暴露与 WTC EHC 计划中登记的当地社区成员的乳腺癌之间存在潜在的表观遗传联系。
