Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes

Authors

Anders Berglund, Moffitt Cancer Center
Kosj Yamoah, Moffitt Cancer Center
Steven A. Eschrich, Moffitt Cancer Center
Rana Falahat, Moffitt Cancer Center
James J. Mulé, Moffitt Cancer Center
Sungjune Kim, Mayo Clinic in Jacksonville, Florida
Jaime Matta, Ponce Health Sciences School of Medicine
Julie Dutil, Ponce Health Sciences School of Medicine
Gilberto Ruiz-Deya, Ponce Health Sciences School of Medicine
Carmen Ortiz Sanchez, Ponce Health Sciences School of Medicine
Liang Wang, Moffitt Cancer Center
Hyun Park, Moffitt Cancer Center
Hirendra N. Banerjee, Elizabeth City State University
Tamara Lotan, Johns Hopkins University
Kathryn Hughes Barry, University of Maryland School of Medicine
Ryan M. Putney, Moffitt Cancer Center
Seung Joon Kim, The Catholic University of Korea Seoul St. Mary's Hospital
Clement Gwede, Moffitt Cancer Center
Jacob K. Kresovich, Moffitt Cancer Center
Youngchul Kim, Moffitt Cancer Center
Hui Yi Lin, LSU Health Sciences Center - New OrleansFollow
Jasreman Dhillon, Moffitt Cancer Center
Ratna Chakrabarti, UCF College of Medicine
Jong Y. Park, Moffitt Cancer Center

Document Type

Article

Publication Date

8-20-2024

Publication Title

Cancer Medicine

Abstract

Introduction: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. Methods: 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. Results: 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. Conclusion: 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.

PubMed ID

39162297

Volume

13

Issue

16

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Berglund, Anders; Yamoah, Kosj; Eschrich, Steven A.; Falahat, Rana; Mulé, James J.; Kim, Sungjune; Matta, Jaime; Dutil, Julie; Ruiz-Deya, Gilberto; Ortiz Sanchez, Carmen; Wang, Liang; Park, Hyun; Banerjee, Hirendra N.; Lotan, Tamara; Barry, Kathryn Hughes; Putney, Ryan M.; Kim, Seung Joon; Gwede, Clement; Kresovich, Jacob K.; Kim, Youngchul; Lin, Hui Yi; Dhillon, Jasreman; Chakrabarti, Ratna; and Park, Jong Y., "Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes" (2024). School of Public Health Faculty Publications. 416.
https://digitalscholar.lsuhsc.edu/soph_facpubs/416
10.1002/cam4.70044