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Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer
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-expos...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105091/ https://www.ncbi.nlm.nih.gov/pubmed/35564499 http://dx.doi.org/10.3390/ijerph19095104 |
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author | Tuminello, Stephanie Zhang, Yian Yang, Lei Durmus, Nedim Snuderl, Matija Heguy, Adriana Zeleniuch-Jacquotte, Anne Chen, Yu Shao, Yongzhao Reibman, Joan Arslan, Alan A. |
author_facet | Tuminello, Stephanie Zhang, Yian Yang, Lei Durmus, Nedim Snuderl, Matija Heguy, Adriana Zeleniuch-Jacquotte, Anne Chen, Yu Shao, Yongzhao Reibman, Joan Arslan, Alan A. |
author_sort | Tuminello, Stephanie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9105091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91050912022-05-14 Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer Tuminello, Stephanie Zhang, Yian Yang, Lei Durmus, Nedim Snuderl, Matija Heguy, Adriana Zeleniuch-Jacquotte, Anne Chen, Yu Shao, Yongzhao Reibman, Joan Arslan, Alan A. Int J Environ Res Public Health Article 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. MDPI 2022-04-22 /pmc/articles/PMC9105091/ /pubmed/35564499 http://dx.doi.org/10.3390/ijerph19095104 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tuminello, Stephanie Zhang, Yian Yang, Lei Durmus, Nedim Snuderl, Matija Heguy, Adriana Zeleniuch-Jacquotte, Anne Chen, Yu Shao, Yongzhao Reibman, Joan Arslan, Alan A. Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer |
title | Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer |
title_full | Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer |
title_fullStr | Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer |
title_full_unstemmed | Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer |
title_short | Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer |
title_sort | global dna methylation profiles in peripheral blood of wtc-exposed community members with breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105091/ https://www.ncbi.nlm.nih.gov/pubmed/35564499 http://dx.doi.org/10.3390/ijerph19095104 |
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