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

Gyorgy Petrovics, Douglas K. Price, Hong Lou, Yongmei Chen, Lisa Garland, Sara Bass, Kristine Jones, Indu Kohaar, Amina Ali, Lakshmi Ravindranath, Denise Young, Jennifer Cullen, Tiffany H. Dorsey, Isabell A. Sesterhenn, Stephen A. Brassell, Inger L. Rosner, Doug Ross, William Dahut, Stefan Ambs, William Douglas FiggShiv Srivastava, Michael Dean*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish
Pages (from-to)406-410
Number of pages5
JournalProstate Cancer and Prostatic Diseases
Volume22
Issue number3
DOIs
StatePublished - 1 Sep 2019
Externally publishedYes

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