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

Table 2. Case Series ofBRCAMutations in Prostate Cancer continued...

In the Washington Ashkenazi Study (WAS), a kin-cohort analytic approach was used to estimate the cumulative risk of prostate cancer among more than 5,000 American AJ male volunteers from the Washington, District of Columbia area who carried one of the BRCA Ashkenazi founder mutations. The cumulative risk to age 70 years was estimated to be 16% (95% CI, 4–30) among carriers and 3.8% among noncarriers (95% CI, 3.3–4.4).[12] This fourfold increase in prostate cancer risk was equal (in absolute terms) to the cumulative risk of ovarian cancer among female mutation carriers at the same age (16% by the age of 70 years; 95% CI, 6–28). The risk of prostate cancer in male mutation carriers in the WAS cohort was elevated by age 50 years, was statistically significantly elevated by age 67 years, and increased thereafter with age, suggesting both an overall excess in prostate cancer risk and an earlier age at diagnosis among carriers of Ashkenazi founder mutations. Prostate cancer risk differed depending on the gene, with BRCA1 mutations associated with increasing risk after age 55 to 60 years, reaching 25% by age 70 years, and 41% by age 80 years. In contrast, prostate cancer risk associated with the BRCA2 mutation began to rise at later ages, reaching 5% by age 70 years and 36% by age 80 years (numeric values were provided by the author [written communication, April 2005]).

The studies summarized in Table 3 used similar case-control methods to examine the prevalence of Ashkenazi founder mutations among Jewish men with prostate cancer and found an overall positive association between founder mutation status and prostate cancer risk.

Table 3. Case-Control Studies in Ashkenazi Jewish Populations ofBRCA1andBRCA2and Prostate Cancer Risk

StudyPopulationControlsMutation Frequency (BRCA1)Mutation Frequency (BRCA2)Prostate Cancer Risk (BRCA1)Prostate Cancer Risk (BRCA2)Comments
AJ = Ashkenazi Jewish; CI = confidence interval; MECC = Molecular Epidemiology of Colorectal Cancer; OR = odds ratio; WAS = Washington Ashkenazi Study.
Guisti et al., 2003[13]979 consecutive AJ men from Israel diagnosed with prostate cancer between 1994 and 1995Prevalence of founder mutations compared with age-matched controls >50 years with no history of prostate cancer from the WAS study and the MECC study from IsraelCases: 16 (1.7%)Cases: 14 (1.5%)185delAG: OR, 2.52 (95% CI, 1.05–6.04)OR, 2.02 (95% CI, 0.16–5.72)There was no evidence of unique or specific histopathology findings within the mutation-associated prostate cancers.
Controls: 11 (0.81%)Controls: 10 (0.74%)5282insC: OR, 0.22 (95% CI, 0.16–5.72)
Kirchoff et al., 2004[14]251 unselected AJ men treated for prostate cancer between 2000 and 20021,472 AJ men with no history of cancerCases: 5 (2.0%)Cases: 8 (3.2%)OR, 2.20 (95% CI, 0.72–6.70)OR, 4.78 (95% CI, 1.87–12.25) 
Controls: 12 (0.8%)Controls: 16 (1.1%)
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 cancerCases: 12 (1.2%)Cases: 18 (1.9%)OR, 1.39 (95% CI, 0.60–3.22)OR, 1.92 (95% CI, 0.91–4.07)Gleason score 7–10 prostate cancer was more common inBRCA1mutation carriers (OR, 2.23; 95% CI, 0.84–5.86) andBRCA2mutation carriers (OR, 3.18; 95% CI, 1.62–6.24) than in controls.
Controls: 11 (0.9%)Controls: 12 (1.0%)
Gallagher et al., 2010[16]832 AJ men diagnosed with localized prostate cancer between 1988 and 2007454 AJ men with no history of cancerNoncarriers: 806 (96.9%)Noncarriers: 447 (98.5%)OR, 0.38 (95% CI, 0.05–2.75)OR, 3.18 (95% CI, 1.52–6.66)TheBRCA15382insC founder mutation was not tested in this series, so it is likely that some carriers of this mutation were not identified. Consequently,BRCA1-related risk may be underestimated. Gleason score 7–10 prostate cancer was more common inBRCA2mutation carriers (85%) than in noncarriers (57%);P = .0002.BRCA1/2mutation carriers had significantly greater risk of recurrence and prostate cancer–specific death than did noncarriers.
Cases: 6 (0.7%)Cases: 20 (2.4%)
Controls: 4 (0.9%)Controls: 3 (0.7%)
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Last Updated: February 25, 2014
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