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A twofold increase in BRCA mutation related prostate cancer among Ashkenazi Israelis is not associated with distinctive histopathology
  1. R M Giusti1,
  2. J L Rutter2,
  3. P H Duray3,
  4. L S Freedman4,
  5. M Konichezky5,
  6. J Fisher-Fischbein6,
  7. M H Greene1,
  8. B Maslansky6,
  9. A Fischbein7,
  10. S B Gruber8,
  11. G Rennert9,
  12. R D Ronchetti3,
  13. S M Hewitt3,
  14. J P Struewing2,
  15. J Iscovich7,*
  1. 1Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Bethesda, MD, USA
  2. 2Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
  3. 3Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD
  4. 4Department of Mathematics, Statistics and Computer Science, Bar Ilan University, Ramat Gan, Israel
  5. 5Department of Pathology, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
  6. 6The International Fertility Institute, Ra’anana, Israel
  7. 7Selikoff Center for Environmental Health and Human Development, Ra’anana, Israel
  8. 8Division of Medical Genetics, University of Michigan, Ann Arbor, MI
  9. 9Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel
  1. Correspondence to:
 Dr R Giusti
 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Executive Plaza South, Room 7024, 6120 Executive Boulevard, MSC 7231, Rockville, MD 20852-7231, USA;

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The magnitude of the risk of prostate cancer among Ashkenazi Jewish carriers of the common mutations in the BRCA1 and BRCA2 genes, the so-called Ashkenazi BRCA founder mutations (BRCA1 185delAG and 5382insC, and BRCA2 6174delT), remains uncertain. Two large epidemiological studies have suggested that the cumulative incidence of prostate cancer among male first degree relatives of individuals with a founder mutation may approach 30% by 80 years of age.1,2 Smaller clinical studies have, in general, not demonstrated an increased frequency of founder mutations among Jewish men with prostate cancer.3–6 Only one study to date has examined clinical characteristics of prostate cancer patients with founder mutations.3 In this study, the three BRCA associated tumours that were identified appeared to be associated with biologically more aggressive disease, presenting with higher PSA levels, higher Gleason scores and more advanced stage at diagnosis, than did prostate cancers diagnosed in men without mutations.

Founder BRCA mutations occur in more than 2% of Ashkenazi Jews.1,7,8 Thus, an increased risk of prostate cancer among BRCA carriers, or an aggressive phenotype in BRCA associated prostate cancers, could constitute a significant cancer burden in this group, and would have substantial management implications for male carriers of Ashkenazi founder mutations.

We undertook the current study to obtain a more stable estimate of the Ashkenazi founder mutation rate among Jewish men diagnosed with prostate cancer, and to determine if prostate cancer occurring in carriers of the common Ashkenazi BRCA1 or BRCA2 mutations is associated with distinctive pathological or clinical features. The precedent for this hypothesis is best illustrated by the hereditary renal cancer syndromes, in which recognising specific histological subsets of subjects has facilitated the identification of genetically distinct disorders.9,10

All men newly diagnosed with prostate cancer were identified at sixteen …

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  • * A complete list of the working group members is provided in the Appendix.

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