Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer.
9/11
World Trade Center
breast cancer
environmental exposure
epigenome-wide association study
exposure assessment
methylation
pathway analysis
Journal
International journal of environmental research and public health
ISSN: 1660-4601
Titre abrégé: Int J Environ Res Public Health
Pays: Switzerland
ID NLM: 101238455
Informations de publication
Date de publication:
22 04 2022
22 04 2022
Historique:
received:
13
02
2022
revised:
16
04
2022
accepted:
19
04
2022
entrez:
14
5
2022
pubmed:
15
5
2022
medline:
18
5
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35564499
pii: ijerph19095104
doi: 10.3390/ijerph19095104
pmc: PMC9105091
pii:
doi:
Substances chimiques
Cytoskeletal Proteins
0
IFT74 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : U01 CA182934
Pays : United States
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