Subgroups of familial and aggressive prostate cancer with considerable frequencies of BRCA2 mutations.
BACKGROUND
One of the known risk factors for prostate cancer (PrCa) is germline mutations in the BRCA2 gene. Previous searches for clinical characteristics which could identify a subgroup of patients enriched for mutation carriers revealed early onset and aggressive PrCa as useful parameters, but they are rather unspecific.


METHODS
Identification of BRCA2 mutation carriers by sequencing all exons of BRCA2 in a German cohort of 382 familial PrCa cases and of 92 sporadic PrCa cases with early onset (≤60 years). 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.


RESULTS
Five BRCA2 mutations and ten variants of unknown significance (VUS) were identified. While the VUS were evenly distributed among the groups, mutation carriers were lacking from the sporadic cases and over represented among familial cases with aggressive disease. High prostate specific antigen (PSA) at diagnosis (>20 ng/ml) was the only criterion with significant enrichment of mutation carriers (6.4%, P = 0.0005). In men with aggressive disease, death from PrCa (6.3% including FH of lethal PrCa; P = 0.05) and FH of both prostate and breast cancer (4.8%; P = 0.3) increased the frequency of mutation carriers. Larger studies and/or meta-analyses are needed to validate these parameters.


CONCLUSIONS
We have identified three potentially useful criteria, high PSA, death from PrCa (patient or FH), and aggressive PrCa in combination with FH of breast and prostate cancer. If confirmed, they may become useful for the decision which patients may benefit from BRCA2 testing.
['Maier|Christiane|C|', 'Herkommer|Kathleen|K|', 'Luedeke|Manuel|M|', 'Rinckleb|Antje|A|', 'Schrader|Mark|M|', 'Vogel|Walther|W|']
D000368:Aged D000369:Aged, 80 and over D024682:BRCA2 Protein D005091:Exons D016368:Frameshift Mutation D024522:Genes, BRCA2 D018095:Germ-Line Mutation D005858:Germany D006801:Humans D007610:Kallikreins D008297:Male D008875:Middle Aged D009154:Mutation D020125:Mutation, Missense D017430:Prostate-Specific Antigen D011471:Prostatic Neoplasms
prostate cancer BRCA2 mutation family history BRCA2 sequencing