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Genetics of Prostate Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Genes With Potential Clinical Relevance in Prostate Cancer Risk

Table 4. Case Series ofBRCA1andBRCA2and Prostate Cancer Risk

StudyPopulationMutation Frequency (BRCA1)Mutation Frequency (BRCA2)Prostate Cancer Risk (BRCA1)Prostate Cancer Risk (BRCA2)Comments
CI = confidence interval; MLPA = multiplex ligation-dependent probe amplification; RR = relative risk.
a Estimate calculated using relative risk data in UK general population.
Agalliu et al., 2007[18]290 men (Caucasian, n = 257; African American, n = 33) diagnosed with prostate cancer <55 y and unselected for family historyNot assessed2 (0.69%)Not assessedRR, 7.8 (95% CI, 1.8–9.4)No mutations were found in African American men.
The two men with a mutation reported no family history of breast cancer or ovarian cancer.
Agalliu et al., 2007[19]266 individuals from 194 hereditary prostate cancer families, including 253 men affected with prostate cancer; median age at prostate cancer diagnosis: 58 yNot assessed0 (0%)Not assessedNot assessed31 nonsynonymous variations were identified; no truncating or deleterious mutations were detected.
Tryggvadóttir et al., 2007[20]527 men diagnosed with prostate cancer between 1955 and 2004Not assessed30/527 (5.7%) carried the Icelandic founder mutation 999del5Not assessedNot assessedTheBRCA2999del5 mutation was associated with a lower mean age at prostate cancer diagnosis (69 vs. 74 y;P = .002)
Kote-Jarai et al., 2011[21]1,832 men diagnosed with prostate cancer between ages 36 and 88 y who participated in the UK Genetic Prostate Cancer StudyNot assessedOverall: 19/1,832 (1.03%)Not assessedRR 8.6a(95% CI, 5.1–12.6)MLPA was not used; therefore, the mutation frequency may be an underestimate, given the inability to detect large genomic rearrangements.
Prostate cancer diagnosed ≤55 y: 8/632 (1.27%)
Leongamornlert et al., 2012[22]913 men with prostate cancer who participated in the UK Genetic Prostate Cancer Study; included 821 cases diagnosed between ages 36 and 65 y, regardless of family history, and 92 cases diagnosed >65 y with a family history of prostate cancerAll cases: 4/886 (0.45%)Not assessedRR, 3.75a(95% CI, 1.02–9.6)Not assessedQuality-control assessment after sequencing excluded 27 cases, resulting in 886 included in the final analysis.
Cases ≤65 y: 3/802 (0.37%)

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)

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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