Furthermore, we reviewed the 62 PrCa diagnoses in all HBOC (n = 161) and Lynch syndrome (n = 124) families previously diagnosed at our department, and found five other BRCA2 mutation carriers and two additional MSH2 mutation carriers.
Our findings provide a rationale for the future use of immune oncological approaches in BRCA2-mutated prostate cancer and may encourage efforts to target immunosuppressive T-cell populations to prime tumors for immunotherapy.
Although the increase in risk of developing breast, ovarian, and prostate cancer in BRCA1 and BRCA2 mutation carriers has been studied extensively, its impact on mortality is not well quantified.
Germline mutations of BRCA2 are predicted to account for approximately 35% of families with multiple case, early onset female breast cancer, and they are also associated with an increased risk of male breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.
Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2-mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies.
However, we estimate that <1% of early-onset prostate cancers in the general US Caucasian population can be attributed to these rare disease-associated BRCA2 mutations.
BRCA2 mutation carriers have an increased risk of death and prostate cancer-related death [HR (95% CI) 4.5 (2.12-9.52), P = 8.9 × 10(-5)] by comparison with noncarriers.
As breast and prostate cancer share genetic risk factors, including rare, high-risk mutations (eg, in BRCA2), we hypothesized that some of these heritable methylation marks might also be associated with the risk of prostate cancer.
Several epidemiologic studies have reported that carriers of germline mutations in the BRCA2 gene have an increased risk of prostate cancer, with the highest risk observed in men diagnosed at earlier ages.
Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.
Individuals with a BRCA2 mutation had significantly higher numbers of observed cases versus expected cases for pancreatic cancer in both men and women (SIR, 21.7; 95% confidence interval [CI], 13.1-34.0; P < .001) and for prostate cancer in men (SIR, 4.9; 95% CI, 2.0-10.1; P = .002).
Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases.