Functional Analysis of Genetic Variants in African Americans with Breast Cancer

The goal of this study is to identify and characterize novel genetic variants associated with a predisposition to breast cancer (BCa) in African Americans (AAs) using a family case-family control study design. Variants of unknown clinical significance (VUS) were characterized using bioinformatics tools. Future studies will further characterize select VUSs using in vitro genomic editing methods and functional assays to determine the functional consequences. The targeted sequencing data is made available for 85 actionable cancer genes. These genes have been previously classified with deleterious mutation(s) and whose phenotype results in a specific, defined medical recommendation(s).

• Study Design:
  • Family/Twin/Trios
• Study Type:
  • Affected Sib Pairs
  • Case-Control
  • Exome Sequencing
  • Extended Pedigrees
  • Family
  • Family Linkage
  • Genotype
  • Marker Discovery
  • Parent-Offspring
  • Probands
• Total number of consented subjects: 88
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• Sequence Read Archive
• MeSH
• PMC

These participants were initially recruited from AA women with a primary diagnosis of BCa and a family history of cancer. Additional participants were then recruited from their family members including first-degree, second-degree, and distant relatives in the same lineage.

Eligibility for this study included meeting one or more of the following criteria:

1. Having multiple cases (≥2) of breast or ovarian cancer in the family;
2. Having early onset breast cancer (≤40 years old);
3. Having bilateral breast cancer;
4. Having breast and ovarian cancer in the same individual, or
5. Having male breast cancer in the family. Positive family history was defined as having multiple cases (≥2) of breast or ovarian cancer in the same side of the family.

DNA samples were from the African American Familial Breast Cancer Study (AAFBC) (citations below) and from the Breast Cancer Determinants in Women from Washington, D.C. study. The original study was approved by the Howard University Institutional Review Board (IRB97CC01). This study met the criteria for exemption as a secondary analysis of existing data was performed and the data were analyzed anonymously and was also approved by the Howard University Institutional Review Board (09-MED-86).

• Panguluri RC, et al.,1999, PMID: 10480351
• Kanaan Y, et al., 2003, PMID: 12942367
• Olopade OI, et al., 2003, PMID: 12491487
• Mefford HC, et al., 1999, PMID: 10417303
  

• Primary Phenotype: Breast Neoplasms
• Breast Cancer, Familial [Supplementary Concept]
• Hereditary Breast and Ovarian Cancer Syndrome

• Principal Investigators
  • Luisel Ricks-Santi, PhD. University of Florida, Gainesville, FL, USA.
  • J. Tyson McDonald, PhD. Georgetown University, Washington DC, USA.
• Funding Source
  • R15CA239100. National Institutes of Health, Bethesda, MD, USA.