Increased frequency of germline BRCA2 mutations associates with prostate cancer metastasis in a racially diverse patient population
| Autor: | Sara Bass, Shiv Srivastava, Gyorgy Petrovics, Michael Dean, Kristine Jones, Hong Lou, Yongmei Chen, Stefan Ambs, Lisa Garland, Isabell A. Sesterhenn, Amina Ali, Jennifer Cullen, William D. Figg, Denise Young, William L. Dahut, Stephen A Brassell, Inger L. Rosner, Tiffany H. Dorsey, Lakshmi Ravindranath, Douglas K. Price, Doug Ross, Indu Kohaar |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Time Factors endocrine system diseases Urology DNA Mutational Analysis 030232 urology & nephrology Disease White People Article Germline Metastasis Cancer screening 03 medical and health sciences Prostate cancer 0302 clinical medicine Germline mutation Internal medicine medicine Humans skin and connective tissue diseases Cancer genetics Gene Germ-Line Mutation Neoplasm Staging BRCA2 Protein Prostatectomy BRCA1 Protein business.industry Prostate Case-control study Prostatic Neoplasms Middle Aged medicine.disease Black or African American Case-Control Studies 030220 oncology & carcinogenesis Disease Progression Prostate surgery Neoplasm Grading Neoplasm Recurrence Local business Follow-Up Studies |
| Zdroj: | Prostate Cancer and Prostatic Diseases |
| ISSN: | 1476-5608 1365-7852 |
| DOI: | 10.1038/s41391-018-0114-1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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