title: DNA methylation profiles in African American prostate cancer patients in relation to disease progression.
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.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States. Electronic address: rrubicz@fredhutch.org.
authors.forename: Rohina
authors.initials: R
authors.lastname: Rubicz
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Milan
authors.initials: M
authors.lastname: Geybels
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Urology, University of Washington School of Medicine, Seattle, WA, United States.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Wright
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kolb
authors.affiliation: Illumina, Inc., San Diego, CA, United States.
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.affiliation: Illumina, Inc., San Diego, CA, United States.
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.affiliation: Department of Pathology, Eastern Virginia Medical School, Norfolk, VA, United States; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, United States.
authors.forename: Dean
authors.initials: D
authors.lastname: Troyer
authors.affiliation: Department of Urology, Eastern Virginia Medical School, Norfolk, VA, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Lance
authors.affiliation: Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, United States.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Ostrander
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Illumina, Inc., San Diego, CA, United States.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stanford
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D018450:Disease Progression; D057890:Epigenomics; D000076610:Genetic Profile; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000077982:Progression-Free Survival; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000628:therapy
keywords: African American; Aggressiveness; DNA methylation; Prostate cancer; Recurrence; Tumor tissue