Germline BRCA mutations denote a clinicopathologic subset of prostate cancer Journal Article

Authors: Gallagher, D. J.; Gaudet, M. M.; Pal, P.; Kirchhoff, T.; Balistreri, L.; Vora, K.; Bhatia, J.; Stadler, Z.; Fine, S. W.; Reuter, V.; Zelefsky, M.; Morris, M. J.; Scher, H. I.; Klein, R. J.; Norton, L.; Eastham, J. A.; Scardino, P. T.; Robson, M. E.; Offit, K.
Article Title: Germline BRCA mutations denote a clinicopathologic subset of prostate cancer
Abstract: Purpose: Increased prostate cancer risk has been reported for BRCA mutation carriers, but BRCA-associated clinicopathologic features have not been clearly defined. Experimental Design: We determined BRCA mutation prevalence in 832 Ashkenazi Jewish men diagnosed with localized prostate cancer between 1988 and 2007 and 454 Ashkenazi Jewish controls and compared clinical outcome measures among 26 BRCA mutation carriers and 806 noncarriers. Kruskal-Wallis tests were used to compare age of diagnosis and Gleason score, and logistic regression models were used to determine associations between carrier status, prostate cancer risk, and Gleason score. Hazard ratios (HR) for clinical end points were estimated using Cox proportional hazards models. Results: BRCA2 mutations were associated with a 3-fold risk of prostate cancer [odds ratio, 3.18; 95% confidence interval (95% CI), 1.52-6.66; P = 0.002] and presented with more poorly differentiated (Gleason score ≥7) tumors (85% versus 57%; P = 0.0002) compared with non-BRCA-associated prostate cancer. BRCA1 mutations conferred no increased risk. After 7,254 person-years of follow-up, and adjusting for clinical stage, prostate-specific antigen, Gleason score, and treatment, BRCA2 and BRCA1 mutation carriers had a higher risk of recurrence [HR (95% CI), 2.41 (1.23-4.75) and 4.32 (1.31-13.62), respectively] and prostate cancer-specific death [HR (95% CI), 5.48 (2.03-14.79) and 5.16 (1.09-24.53), respectively] than noncarriers. Conclusions: BRCA2 mutation carriers had an increased risk of prostate cancer and a higher histologic grade, and BRCA1 or BRCA2 mutations were associated with a more aggressive clinical course. These results may have implications for tailoring clinical management of this subset of hereditary prostate cancer. ©2010 AACR.
Keywords: adult; controlled study; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; case-control studies; clinical feature; histopathology; cancer localization; cancer risk; adenocarcinoma; genetic predisposition to disease; prevalence; gene frequency; odds ratio; risk factors; brca1 protein; brca2 protein; heterozygote; cancer mortality; gleason score; prostatic neoplasms; genes, brca1; genes, brca2; prostate adenocarcinoma; germ-line mutation; heterozygote detection
Journal Title: Clinical Cancer Research
Volume: 16
Issue: 7
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2010-04-01
Start Page: 2115
End Page: 2121
Language: English
DOI: 10.1158/1078-0432.ccr-09-2871
PUBMED: 20215531
PROVIDER: scopus
PMCID: PMC3713614
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus"
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MSK Authors
  1. Kenneth Offit
    507 Offit
  2. Michael J Zelefsky
    615 Zelefsky
  3. Larry Norton
    557 Norton
  4. Michael Morris
    274 Morris
  5. Mark E Robson
    365 Robson
  6. Peter T Scardino
    621 Scardino
  7. Prodipto Pal
    6 Pal
  8. Zsofia Kinga Stadler
    144 Stadler
  9. James Eastham
    426 Eastham
  10. Robert J. Klein
    59 Klein
  11. Samson W Fine
    315 Fine
  12. Victor Reuter
    899 Reuter
  13. Howard Scher
    816 Scher
  14. Kinjal C Vora
    25 Vora
  15. Jasmine Bhatia
    11 Bhatia
  16. Mia Gaudet
    16 Gaudet