Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer

Benjamin A. Rybicki, Andrew Rundle, Oleksandr Kryvenko, Nicoleta Mitrache, Kieu C. Do, Michelle Jankowski, Dhananjay A. Chitale, Sheri Trudeau, Steven A. Belinsky, Deliang Tang

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2884-2893
Number of pages10
JournalInternational Journal of Cancer
Volume138
Issue number12
DOIs
StatePublished - Jun 15 2016

Fingerprint

Methylation
Disease Progression
Prostate
Prostatic Neoplasms
Recurrence
APC Genes
Genes
Unnecessary Procedures
Prostate-Specific Antigen
Prostatectomy
Genetic Promoter Regions
African Americans
Radiotherapy
Biomarkers
Biopsy
DNA
Neoplasms

Keywords

  • biomarkers
  • biopsy
  • disease recurrence
  • DNA methylation
  • field cancerization

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer. / Rybicki, Benjamin A.; Rundle, Andrew; Kryvenko, Oleksandr; Mitrache, Nicoleta; Do, Kieu C.; Jankowski, Michelle; Chitale, Dhananjay A.; Trudeau, Sheri; Belinsky, Steven A.; Tang, Deliang.

In: International Journal of Cancer, Vol. 138, No. 12, 15.06.2016, p. 2884-2893.

Research output: Contribution to journalArticle

Rybicki, BA, Rundle, A, Kryvenko, O, Mitrache, N, Do, KC, Jankowski, M, Chitale, DA, Trudeau, S, Belinsky, SA & Tang, D 2016, 'Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer', International Journal of Cancer, vol. 138, no. 12, pp. 2884-2893. https://doi.org/10.1002/ijc.30038
Rybicki, Benjamin A. ; Rundle, Andrew ; Kryvenko, Oleksandr ; Mitrache, Nicoleta ; Do, Kieu C. ; Jankowski, Michelle ; Chitale, Dhananjay A. ; Trudeau, Sheri ; Belinsky, Steven A. ; Tang, Deliang. / Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer. In: International Journal of Cancer. 2016 ; Vol. 138, No. 12. pp. 2884-2893.
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