Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population.
Prostate Cancer Prostatic Dis
; 22(3): 406-410, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-30542053
ABSTRACT
BACKGROUND:
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.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Prostatectomia
/
Neoplasias da Próstata
/
Proteína BRCA2
/
Recidiva Local de Neoplasia
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Prostate Cancer Prostatic Dis
Assunto da revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
/
UROLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos