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

Author:

Berglund Anders1ORCID,Yamoah Kosj2ORCID,Eschrich Steven A.1ORCID,Falahat Rana3,Mulé James J.3,Kim Sungjune4,Matta Jaime5,Dutil Julie5,Ruiz‐Deya Gilberto5,Ortiz Sanchez Carmen5,Wang Liang6,Park Hyun7,Banerjee Hirendra N.8,Lotan Tamara9,Barry Kathryn Hughes1011,Putney Ryan M.1,Kim Seung Joon12ORCID,Gwede Clement13,Kresovich Jacob K.7,Kim Youngchul1,Lin Hui‐Yi14,Dhillon Jasreman15,Chakrabarti Ratna16,Park Jong Y.7ORCID

Affiliation:

1. Department of Biostatistics and Bioinformatics H. Lee Moffitt Cancer Center Tampa Florida USA

2. Department of Radiation Oncology H. Lee Moffitt Cancer Center Tampa Florida USA

3. Department of Immunology H. Lee Moffitt Cancer Center Tampa Florida USA

4. Department of Radiation Oncology Mayo Clinic Alix College of Medicine and Health Sciences Jacksonville Florida USA

5. Department of Basic Sciences Ponce Research Institute, Ponce Health Sciences University‐School of Medicine Ponce Puerto Rico

6. Department of Tumor Biology H. Lee Moffitt Cancer Center Tampa Florida USA

7. Department of Cancer Epidemiology H. Lee Moffitt Cancer Center Tampa Florida USA

8. Natural, Pharmacy and Health Sciences Elizabeth City State University Elizabeth City North Carolina USA

9. Johns Hopkins University Baltimore Maryland USA

10. Department of Epidemiology and Public Health University of Maryland School of Medicine Baltimore Maryland USA

11. Program in Oncology University of Maryland Greenebaum Comprehensive Cancer Center Baltimore Maryland USA

12. Division of Pulmonology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea Seoul Republic of Korea

13. Department of Health Outcome and Behavior H. Lee Moffitt Cancer Center Tampa Florida USA

14. Biostatistics and Data Science Program, School of Public Health Louisiana State University School of Medicine New Orleans Louisiana USA

15. Department of Pathology H. Lee Moffitt Cancer Center Tampa Florida USA

16. Burnett School of Biomedical Sciences University of Central Florida Orlando Florida USA

Abstract

AbstractIntroductionMen with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.MethodsThis 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.ResultsAround 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.ConclusionSeveral 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.

Funder

Division of Cancer Prevention, National Cancer Institute

DOD Prostate Cancer Research Program

Common Fund

Publisher

Wiley

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