Although multiple genes have been implicated in the development of PCa, few confer as high a risk as mutations in the genes associated with early-onset breast cancer (BRCA1 and BRCA2).
To define a subgroup of PrCa patients enriched for BRCA2 mutation carriers, we used clinical parameters including a detailed family history (FH) for PrCa and breast cancer.
Germline mutations of BRCA2 and NBS1 genes cause inherited recessive chromosomal instability syndromes and predispose to prostate cancer of poor prognosis.
The present study strengthens the known links between BRCA2 and pancreatic and prostate cancer, but throws further doubt onto any association with BRCA1.
Germline mutations in the breast cancer predisposition gene 2 (BRCA2) are the genetic events known to date that confer the highest risk of prostate cancer (8.6-fold in men ≤65 years).
Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study.
Decreased frequency and intensity of nuclear BRCA2 labeling were inversely correlated with Skp2 expression in high-grade prostatic intraepithelial neoplasia and PCa.
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.
These results suggest that routine testing of early onset PrCa cases for germline BRCA2 mutations will further help to refine the prevalence and risk associated with BRCA2 mutations and may be useful for guiding management options.
To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited.
BRCA2 mutation carriers had an increased risk of prostate cancer and a higher histologic grade, and BRCA1 or BRCA2 mutations were associated with a more aggressive clinical course.
Additional findings, regardless of TMPRSS2-ERG status, were the overrepresentation of a rare BRCA2 variant (V2728I: P = 0.03; OR, 6.16; 95% CI, 1.19-32.00) in familial PCa and of a common allele of RMI1 (variant N455S: P = 0.02; OR, 1.33; 95% CI, 1.04-1.70) in unselected PCa cases.
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.