Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.


Germline mutations in BRCA2 have been linked to a higher risk of prostate cancer (PCa), and high frequency of BRCA1 and BRCA2 (BRCA1/2) gene alterations was recently reported in metastatic castration-resistant PCa specimens. Mutations in BRCA2 vary in racial and ethnic groups including African-American (AA) and Caucasian-American (CA) populations.

BRCA1 and BRCA2 genes were sequenced (Ion AmpliSeq targeted sequencing) in archived blood DNA specimens in 1240 PCa patients, including 30% AA patients, in three different cohorts: localized early stage (T2) PCa (N = 935); advanced PCa (50% T3-4) (N = 189); and metastatic PCa (N = 116). The sequences were analyzed for known and novel mutations in BRCA1/2. Statistical analyses were performed to determine associations of the mutations with clinico-pathological parameters.

BRCA2 mutations with known pathogenic annotation were significantly more prevalent in men with advanced and metastatic PCa (3.1%) compared to patients with an organ-confined disease (0.7%). AA patients carried more frequently BRCA1/2 variants of unknown significance (VUS) when compared to Caucasian Americans (4.6 vs. 1.6%, respectively). Significantly, pathogenic BRCA2 mutations in men with localized early stage PCa increased the risk of distant metastasis.

Germline variants of unknown significance in BRCA1/2 are more frequent in AA than CA PCa patients; however, the prevalence of pathogenic mutations were similar across the races. Patients carrying BRCA2 pathogenic mutations are more likely to progress to metastasis.

  • Ali A
  • Ambs S
  • Bass S
  • Brassell SA
  • Chen Y
  • Cullen J
  • Dahut W
  • Dean M
  • Dorsey TH
  • Figg WD
  • Garland L
  • Jones K
  • Kohaar I
  • Lou H
  • Petrovics G
  • Price DK
  • Ravindranath L
  • Rosner IL
  • Ross D
  • Sesterhenn IA
  • Srivastava S
  • Young D
PubMed ID
Appears In
Prostate Cancer Prostatic Dis, 2019, 22 (3)