Methylation of the RARB gene increases prostate cancer risk in black Americans

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

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Purpose: Gene promoter hypermethylation may be useful as a biomarker for cancer risk in histopathologically benign prostate specimens. Materials and Methods: We performed a nested case-control study of gene promoter methylation status for 5 genes (APC, RARB, CCND2, RASSF1 and MGMT) measured in benign biopsy specimens from 511 prostate cancer case-control pairs. We estimated the overall and race stratified risk of subsequent prostate cancer associated with methylation status. Results: On race stratified analysis RARB methylation was associated with a higher cancer risk in black American men (OR 2.18, 95% CI 1.39-3.44). APC methylation was associated with an increased risk of high grade tumors (OR 2.43, 95% CI 1.20-4.90), which was higher in black than in white men (OR 3.21 vs 2.04). In cases RARB and APC gene methylation in benign prostate samples persisted in matched malignant specimens. In black cases the combined risk associated with RARB and APC methylation (OR 3.04, 95% CI 1.44-6.42) was greater than the individual risk of each gene and significantly different from that in white cases (OR 1.14, 95% CI 0.56-2.30). Conclusions: RARB gene methylation in histopathologically benign prostate samples was associated with a statistically significant increased risk of subsequent prostate cancer in black men. Methylation data on additional genes may improve risk stratification and clinical decision making algorithms for cancer screening and diagnosis.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalJournal of Urology
Volume190
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

Keywords

  • African Americans
  • DNA methylation
  • prostate
  • prostatic neoplasms
  • risk

ASJC Scopus subject areas

  • Urology

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    Tang, D., Kryvenko, O. N., Mitrache, N., Do, K. C., Jankowski, M., Chitale, D. A., Trudeau, S., Rundle, A., Belinsky, S. A., & Rybicki, B. A. (2013). Methylation of the RARB gene increases prostate cancer risk in black Americans. Journal of Urology, 190(1), 317-324. https://doi.org/10.1016/j.juro.2013.01.083