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

Table 11. Case-Control Studies ofBRCA1andBRCA2and Prostate Cancer Aggressiveness continued...

These studies suggest that prostate cancer in BRCA mutation carriers may be associated with features of aggressive disease, including higher Gleason score, higher prostate-specific antigen (PSA) level at diagnosis, and higher tumor stage and/or grade at diagnosis, a finding that warrants consideration as patients undergo cancer risk assessment and genetic counseling.

BRCA1/BRCA2and survival outcomes

Analyses of prostate cancer cases in families with known BRCA1 or BRCA2 mutations have been examined for survival. In an unadjusted analysis performed on a case series, median survival was 4 years in 183 men with prostate cancer with a BRCA2 mutation and 8 years in 119 men with a BRCA1 mutation. The study suggests that BRCA2 mutation carriers have a poorer survival than BRCA1 mutation carriers.[29] To further assess this observation, case-control studies were conducted (summarized in Table 12).

Table 12. Case-Control Studies ofBRCA1andBRCA2and Survival Outcomes

Study Population Controls Prostate Cancer-Specific Survival Overall Survival Comments
CI = confidence interval; HR = hazard ratio; PSA = prostate-specific antigen.
Tryggvadóttir et al. (2007)[23] 30 men diagnosed with prostate cancer who wereBRCA2999del5 founder mutation carriers 59 men with prostate cancer matched by birth and diagnosis year and confirmed not to carry theBRCA2999del5 mutation BRCA2999del5 mutation was associated with a higher risk of death from prostate cancer (HR, 3.42; 95% CI, 2.12-5.51), which remained after adjustment for tumor stage and grade (HR, 2.35; 95% CI, 1.08-5.11). Not assessed
Edwards et al. (2010)[26] 21 men diagnosed with prostate cancer who harbored aBRCA2mutation: 6 with early-onset disease (≤55 y) from a UK prostate cancer study and 15 unselected for age at diagnosis from a UK clinical series 1,587 age- and stage-matched men with prostate cancer Not assessed Overall survival was lower inBRCA2mutation carriers (4.8 y) than in noncarriers (8.5 y); in noncarriers, HR, 2.14 ( 95% CI, 1.28-3.56;P = .003).
Gallagher et al. (2010)[16] 832 AJ men diagnosed with localized prostate cancer between 1988 and 2007, of which there were 6BRCA1mutation carriers and 20BRCA2mutation carriers 454 AJ men with no history of cancer After adjusting for stage, PSA, Gleason score, and therapy received: Not assessed TheBRCA15382insC founder mutation was not tested in this series.
-BRCA1 185delAG mutation carriers had a greater risk of death due to prostate cancer (HR, 5.16; 95% CI, 1.09-24.53;P = .001).
- BRCA26174delT mutation carriers had a greater risk of death due to prostate cancer (HR, 5.48; 95% CI, 2.03-14.79;P = .001).
Thorne et al. (2011)[27] 40 men diagnosed with prostate cancer who were BRCA2 mutation carriers from 30 familial breast cancer families from Australia and New Zealand 97 men from 89 familial breast cancer families from Australia and New Zealand with prostate cancer and noBRCAmutation found in the family BRCA2carriers were shown to have an increased risk of prostate cancer-specific mortality (HR, 4.5; 95% CI, 2.12-9.52;P = 8.9 × 10-5), compared with noncarrier controls. BRCA2carriers were shown to have an increased risk of death (HR, 3.12; 95% CI, 1.64-6.14;P = 3.0 × 10-4), compared with noncarrier controls. There were too fewBRCA1carriers available to include in the analysis.
Castro et al. (2013)[28] 2,019 men diagnosed with prostate cancer from the United Kingdom, of whom 18 wereBRCA1mutation carriers and 61 wereBRCA2mutation carriers 1,940 men who wereBRCA1/2noncarriers Prostate cancer-specific survival at 5 years: Overall survival at 5 years: For localized prostate cancer, metastasis-free survival was also higher in controls than in mutation carriers (93% vs. 77%; HR, 2.7).
- BRCA1: 80.8 (95% CI, 56.9-100) - BRCA1: 82.5 (95% CI, 60.4-100)
-BRCA2: 67.9 (95% CI 53.4-82.4) -BRCA2: 57.9 (95% CI, 43.4-72.4)
- Controls: 90.6 (95% CI 88.8-92.4) - Controls: 86.4 (95% CI, 84.4-88.4)
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