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DNA methylation profiles in African American prostate cancer patients in relation to disease progression
Authors:Rohina Rubicz  Shanshan Zhao  Milan Geybels  Jonathan L Wright  Suzanne Kolb  Brandy Klotzle  Marina Bibikova  Dean Troyer  Raymond Lance  Elaine A Ostrander  Ziding Feng  Jian-Bing Fan  Janet L Stanford
Institution:1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States;2. Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States;3. Department of Urology, University of Washington School of Medicine, Seattle, WA, United States;4. Illumina, Inc., San Diego, CA, United States;5. Department of Pathology, Eastern Virginia Medical School, Norfolk, VA, United States;6. Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States;7. Department of Urology, Eastern Virginia Medical School, Norfolk, VA, United States;8. Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, United States;9. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, United States;10. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States
Abstract:This study examined whether differential DNA methylation is associated with clinical features of more aggressive disease at diagnosis and prostate cancer recurrence in African American men, who are more likely to die from prostate cancer than other populations. Tumor tissues from 76 African Americans diagnosed with prostate cancer who had radical prostatectomy as their primary treatment were profiled for epigenome-wide DNA methylation levels. Long-term follow-up identified 19 patients with prostate cancer recurrence. Twenty-three CpGs were differentially methylated (FDR q  0.25, mean methylation difference  0.10) in patients with vs. without recurrence, including CpGs in GCK, CDKL2, PRDM13, and ZFR2. Methylation differences were also observed between men with metastatic-lethal prostate cancer vs. no recurrence (five CpGs), regional vs. local pathological stage (two CpGs), and higher vs. lower tumor aggressiveness (one CpG). These results indicate that differentially methylated CpG sites identified in tumor tissues of African American men may contribute to prostate cancer aggressiveness.
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