Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.
epidemiology
epigenetics
methylation
prostate cancer
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
revised:
13
06
2024
received:
04
04
2024
accepted:
12
07
2024
medline:
20
8
2024
pubmed:
20
8
2024
entrez:
20
8
2024
Statut:
ppublish
Résumé
Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔβl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔβl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa. Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70044Subventions
Organisme : Division of Cancer Prevention, National Cancer Institute
ID : K07CA230182
Organisme : Division of Cancer Prevention, National Cancer Institute
ID : P30-CA076292
Organisme : DOD Prostate Cancer Research Program
ID : HT9425-23-1-0650
Organisme : DOD Prostate Cancer Research Program
ID : HT9425-23-1-0651
Organisme : Florida Department of Health, James and Esther King Biomedical Research Program
ID : 6JK06
Organisme : Maryland Department of Health's Cigarette Restitution Fund Program
ID : CH-649-CRF
Organisme : Common Fund
ID : U54CA163068
Informations de copyright
© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.
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