title: Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.
abstract: In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease.
authors: Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI.|Josephine Ford Cancer Institute, Henry Ford Hospital, Detroit, MI.
authors: Benjamin A
authors: BA
authors: Rybicki
authors: Department of Epidemiology, Columbia University, New York, NY.
authors: Andrew
authors: A
authors: Rundle
authors: Department of Pathology and Urology, University of Miami Miller School of Medicine, Miami, FL.
authors: Oleksandr N
authors: ON
authors: Kryvenko
authors: Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI.
authors: Nicoleta
authors: N
authors: Mitrache
authors: Lung Cancer Division, Lovelace Respiratory Research Institute, Albuquerque, NM.
authors: Kieu C
authors: KC
authors: Do
authors: Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI.
authors: Michelle
authors: M
authors: Jankowski
authors: Josephine Ford Cancer Institute, Henry Ford Hospital, Detroit, MI.|Department of Surgical Pathology, Henry Ford Hospital, Detroit, MI.
authors: Dhananjay A
authors: DA
authors: Chitale
authors: Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI.
authors: Sheri
authors: S
authors: Trudeau
authors: Lung Cancer Division, Lovelace Respiratory Research Institute, Albuquerque, NM.
authors: Steven A
authors: SA
authors: Belinsky
authors: Department of Environmental Health Sciences, Columbia University, New York, NY.
authors: Deliang
authors: D
authors: Tang
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011467:Prostate / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA
keywords: DNA methylation; biomarkers; biopsy; disease recurrence; field cancerization