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Genes With Potential Clinical Relevance in Prostate Cancer Risk

    Table 4. Case Series ofBRCA1andBRCA2and Prostate Cancer Risk continued...

    These case series confirm that mutations in BRCA1 and BRCA2 do not play a significant role in hereditary prostate cancer. However, germline mutations in BRCA2 account for some cases of early-onset prostate cancer, although this is estimated to be less than 1% of early-onset prostate cancers in the United States.[18]

    Prostate cancer aggressiveness inBRCAmutation carriers

    The studies summarized in Table 5 used similar case-control methods to examine features of prostate cancer aggressiveness among men with prostate cancer found to harbor a BRCA1/BRCA2 mutation.

    Table 5. Case-Control Studies ofBRCA1andBRCA2and Prostate Cancer Aggressiveness

    StudyPopulationControlsGleason ScoreaPSAaTumor Stage or GradeaComments
    AJ = Ashkenazi Jewish; CI = confidence interval; HR = hazard ratio; OR = odds ratio; PSA = prostate-specific antigen.
    a Measures of prostate cancer aggressiveness.
    Tryggvadóttir et al., 2007[20]30 men diagnosed with prostate cancer who wereBRCA2999del5 founder mutation carriers59 men with prostate cancer matched by birth and diagnosis year and confirmed not to carry theBRCA2999del5 mutationGleason score 7–10:Not assessedStage IV at diagnosis: 
    Cases: 84%Cases: 55.2%
    Controls: 52.7%Controls: 24.6%
    Agalliu et al., 2009[15]979 AJ men diagnosed with prostate cancer between 1978 and 2005 (mean and median year of diagnosis: 1996)1,251 AJ men with no history of cancerGleason score 7–10:Not assessedNot assessed 
    BRCA1185delAG mutation: OR, 3.54 (95% CI, 1.22–10.31)
    BRCA26174delT mutation: OR, 3.18 (95% CI, 1.37–7.34)
    Edwards et al., 2010[23]21 men diagnosed with prostate cancer who harbored aBRCA2 mutation: 6 with early-onset disease (≤55 y) from a UK prostate cancer study and 15 unselected for age at diagnosis from a UK clinical series1,587 age- and stage-matched men with prostate cancerNot assessedPSA ≥25 ng/mL: HR, 1.39 (95% CI, 1.04–1.86)Stage T3: HR, 1.19 (95% CI, 0.68–2.05) 
    Stage T4: HR, 1.87 (95% CI, 1.00–3.48)
    Grade 2: HR, 2.24 (95% CI, 1.03–4.88)
    Grade 3: HR, 3.94 (95% CI, 1.78–8.73)
    Gallagher et al., 2010[16]832 AJ men diagnosed with localized prostate cancer between 1988 and 2007, of which there were sixBRCA1mutation carriers and 20BRCA2mutation carriers454 AJ men with no history of cancerGleason score 7–10:Not assessedNot assessedTheBRCA15382insC founder mutation was not tested in this series.
    BRCA26174delT mutation: HR, 2.63 (95% CI, 1.23–5.6;P = .001)
    Thorne et al., 2011[24]40 men diagnosed with prostate cancer who were BRCA2 mutation carriers from 30 familial breast cancer families from Australia and New Zealand97 men from 89 familial breast cancer families from Australia and New Zealand with prostate cancer and noBRCAmutation found in the familyGleason score ≥8:PSA10–100 ng/mL:Stage ≥pT3 at presentation:BRCA2mutation carriers were more likely to have high-risk disease byD'Amico criteriathan were noncarriers (77.5% vs. 58.7%,P = .05).
    BRCA2mutations: 35% (14/40)
    BRCA2mutations: 65.8% (25/38)Controls: 27.9% (27/97)BRCA2mutations: 44.7% (17/38)
    PSA >101 ng/mL:Controls: 22.6% (21/97)
    Controls: 33.0% (25/97)BRCA2mutations: 10% (4/40)
    Controls: 2.1% (2/97)
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