title: Methylation of the RARB gene increases prostate cancer risk in black Americans.
abstract: OBJECTIVE
  Gene promoter hypermethylation may be useful as a biomarker for cancer risk in histopathologically benign prostate specimens.
  
  
  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.
authors: Department of Environmental Health Sciences, Columbia University, New York, New York, USA.
authors: Deliang
authors: D
authors: Tang
authors: Oleksandr N
authors: ON
authors: Kryvenko
authors: Nicoleta
authors: N
authors: Mitrache
authors: Kieu C
authors: KC
authors: Do
authors: Michelle
authors: M
authors: Jankowski
authors: Dhananjay A
authors: DA
authors: Chitale
authors: Sheri
authors: S
authors: Trudeau
authors: Andrew
authors: A
authors: Rundle
authors: Steven A
authors: SA
authors: Belinsky
authors: Benjamin A
authors: BA
authors: Rybicki
mesh_terms: D001741:Black or African American / Q000235:genetics*; D017677:Age Distribution; D000368:Aged; D001707:Biopsy, Needle; D016022:Case-Control Studies; D016001:Confidence Intervals; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D044465:White People / Q000235:genetics
chemical_list: D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta
references: Expert Rev Mol Diagn. 2009 Apr;9(3):243-57
references: 19379083
references: Cancer Epidemiol Biomarkers Prev. 2009 Oct;18(10):2717-22
references: 19755651
references: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
references: 8790415
references: Oncogene. 1999 Feb 11;18(6):1313-24
references: 10022813
references: In Vivo. 1994 May-Jun;8(3):439-43
references: 7803731
references: Clin Cancer Res. 2010 Jul 15;16(14):3539-47
references: 20606036
references: Prostate. 2001 May 1;47(2):111-7
references: 11340633
references: J Urol. 2006 Sep;176(3):1114-7
references: 16890704
references: Cancer Epidemiol Biomarkers Prev. 1998 Jun;7(6):531-6
references: 9641498
references: BJU Int. 2012 Jul;110(1):56-62
references: 22077694
references: J Natl Cancer Inst. 2006 Feb 15;98(4):255-61
references: 16478744
references: Prostate. 2008 Feb 1;68(2):152-60
references: 18058812
references: Front Biosci. 2007 May 01;12:4254-66
references: 17485372
references: Mod Pathol. 2012 Jul;25(7):1023-32
references: 22460812
references: Prostate. 2009 Sep 15;69(13):1470-9
references: 19462462
references: Clin Cancer Res. 2007 Oct 15;13(20):6122-9
references: 17947477
references: Cancer Res. 2004 Mar 15;64(6):1975-86
references: 15026333
references: J Clin Oncol. 2009 Jul 1;27(19):3161-8
references: 19470943
references: PLoS One. 2010 Mar 09;5(3):e9584
references: 20231893
references: Pathobiology. 2010;77(5):260-6
references: 21116117
references: Annu Rev Med. 2012;63:161-70
references: 22053739
references: J Natl Cancer Inst. 2007 Sep 19;99(18):1395-400
references: 17848671
references: J Urol. 2010 May;183(5):1792-6
references: 20299055
references: Prostate. 2003 May 15;55(3):199-205
references: 12692786
references: J Urol. 2013 Jun;189(6):2335-41
references: 23159584
references: Int J Cancer. 2005 Aug 20;116(2):174-81
references: 15800905