Rare germline mutations in African American men diagnosed with early‐onset prostate cancer

• Published in: The Prostate Vol. 78; no. 5; pp. 321 - 326
• Main Authors: Beebe‐Dimmer, Jennifer L., Zuhlke, Kimberly A., Johnson, Anna M., Liesman, Daniel, Cooney, Kathleen A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2018
• Subjects: Adult; African Americans; African Americans - genetics; Ataxia Telangiectasia Mutated Proteins - genetics; ATM; BRCA1; BRCA1 protein; BRCA2; BRCA2 protein; BRCA2 Protein - genetics; BRIP1; Deoxyribonucleic acid; DNA; DNA, Neoplasm - genetics; Fanconi Anemia Complementation Group Proteins - genetics; Genetic diversity; Germ-Line Mutation; Health risk assessment; Humans; Male; Middle Aged; Mismatch Repair Endonuclease PMS2 - genetics; Mutation; Mutation, Missense; Prostate cancer; Prostatic Neoplasms - ethnology; Prostatic Neoplasms - genetics; racial disparities genetic epidemiology; RNA Helicases - genetics; BRIP1; ATM; BRCA1; BRCA2; racial disparities genetic epidemiology
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.23464

Background African Americans have both a higher incidence of prostate cancer and greater disease‐specific mortality compared with non‐Hispanic whites. Historically, the investigation of the contribution of rare genetic variants to prostate cancer in African American men has been hampered by low participation in large genetic studies, particularly those focused on early‐onset and familial disease. Methods We sequenced 160 genes purported to be involved in carcinogenic pathways in germline DNA samples collected from 96 African American men diagnosed with early‐onset prostate cancer (≤55 years at diagnosis). REVEL software was used to determine the pathogenic potential of observed missense variants. Results We observed three protein‐truncating mutations, one in BRCA2 and two in BRIP1 in three African American men diagnosed with early‐onset prostate cancer. Furthermore, we observed five rare, mostly private, missense variants among four genes (BRCA1, BRCA2, PMS2, and ATM) that were predicted to be deleterious and hence likely pathogenic in our patient sample. Conclusions Protein‐truncating mutations in BRCA2 and BRIP1 were discovered in African American men diagnosed with early‐onset prostate cancer. Further study is necessary to determine the role of rare, missense variants to prostate cancer incidence, and progression in this group of high‐risk men.