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. 2019 Sep;22(3):406-410.
doi: 10.1038/s41391-018-0114-1. Epub 2018 Dec 12.

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

Gyorgy Petrovics #  1   2 , Douglas K Price #  3 , Hong Lou #  4 , Yongmei Chen  1 , Lisa Garland  4 , Sara Bass  4 , Kristine Jones  4 , Indu Kohaar  1 , Amina Ali  1   2   5 , Lakshmi Ravindranath  1 , Denise Young  1 , Jennifer Cullen  1   2 , Tiffany H Dorsey  6 , Isabell A Sesterhenn  7 , Stephen A Brassell  1   5   8 , Inger L Rosner  1   2   5 , Doug Ross  3 , William Dahut  3 , Stefan Ambs  6 , William Douglas Figg  3 , Shiv Srivastava  1   2 , Michael Dean  9
Affiliations

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

Gyorgy Petrovics et al. Prostate Cancer Prostatic Dis. 2019 Sep.

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Kaplan–Meier distant metastasis-free survival curves across BRCA1/2 mutation status (cohort 1, N = 927). The figure depicts time to distant metastasis as survival estimate for the categories of patients based on BRCA1/2 mutation status. a Wild-type BRCA1/2 and benign/likely benign mutations in BRCA1/2; b variants of unknown significance in BRCA1/2; c pathogenic mutations in BRCA1/2; d metastasis
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