Sokolowska Katarzyna Ewa, Antoniewski Jacek, Sobalska-Kwapis Marta, Strapagiel Dominik, Marciniak Wojciech, Lubiński Jan, Wojdacz Tomasz Kazimierz
Independent Clinical Epigenetics Laboratory, Pomeranian Medical University, Unii Lubelskiej 1, Szczecin, 71-252, Poland.
Biobank Laboratory, Departament of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 139 St, Lodz, 90-235, Poland.
Int Arch Occup Environ Health. 2025 Aug;98(6):515-523. doi: 10.1007/s00420-025-02147-6. Epub 2025 May 26.
The results of studies assessing impact of arsenic exposure on methylome are to large extent inconsistent. To contribute to understanding of effect of arsenic exposure on methylome of the exposed cells, we assess the impact of low-level arsenic exposure on methylome of blood cells in three cohorts of exposed individuals.
The Infinium MethylationEPIC array (Illumina Inc.) was used for genome-wide methylation profiling and robust linear regression to identify arsenic-related methylation changes in blood cells from healthy individuals with a 12-year cancer-free follow-up and breast cancer patients, sampled on average 4.29 years before diagnosis, as well as methylomics data from cord blood samples of Biomarkers of Exposure to Arsenic cohort.
Our analysis identified a 2,453 arsenic-associated methylation changes in blood from healthy individuals, 9,662 in breast cancer patients and 6,745 in cord blood samples. Similarly to previous studies methylation changes that we identified in each cohort, overlapped only to some extent. However, molecular processes linked to identified methylation changes were very similar in each of the cohorts. And included pathways that could be clearly associated with the adverse effects of arsenic exposure and specifically cancer in the cohort of cancer patients. Moreover, the genomic regions harboring identified in each cohort methylation changes were similar and predominantly included regions participating in regulation of gene transcription.
Overall, our findings show that specificity of arsenic related methylation changes is low but the impact of these changes on cell physiology is very similar across three cohorts we studded.
评估砷暴露对甲基化组影响的研究结果在很大程度上不一致。为了有助于理解砷暴露对暴露细胞甲基化组的影响，我们评估了低水平砷暴露对三组暴露个体血细胞甲基化组的影响。
使用Infinium MethylationEPIC芯片（Illumina公司）进行全基因组甲基化分析，并采用稳健线性回归来识别来自无癌随访12年的健康个体、平均在诊断前4.29年采样的乳腺癌患者血细胞中与砷相关的甲基化变化，以及来自砷暴露生物标志物队列脐带血样本的甲基组学数据。
我们的分析在健康个体血液中鉴定出2453个与砷相关的甲基化变化，在乳腺癌患者中鉴定出9662个，在脐带血样本中鉴定出6745个。与之前的研究类似，我们在每个队列中鉴定出的甲基化变化仅在一定程度上重叠。然而，与鉴定出的甲基化变化相关的分子过程在每个队列中非常相似。并且包括在癌症患者队列中可能与砷暴露的不良影响特别是癌症明显相关的途径。此外，每个队列中鉴定出甲基化变化的基因组区域相似，主要包括参与基因转录调控的区域。
总体而言，我们的研究结果表明，与砷相关的甲基化变化的特异性较低，但这些变化对细胞生理学的影响在我们研究的三个队列中非常相似。
