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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Beebe-Dimmer, JL; Zuhlke, KA; Johnson, AM; Liesman, D; Cooney, KA

Published Date

  • April 2018

Published In

Volume / Issue

  • 78 / 5

Start / End Page

  • 321 - 326

PubMed ID

  • 29356034

Pubmed Central ID

  • 29356034

Electronic International Standard Serial Number (EISSN)

  • 1097-0045

Digital Object Identifier (DOI)

  • 10.1002/pros.23464

Language

  • eng

Conference Location

  • United States