Gene panel screening for insight towards breast cancer susceptibility in different ethnicities

PLoS One. 2020 Aug 31;15(8):e0238295. doi: 10.1371/journal.pone.0238295. eCollection 2020.

Abstract

African American breast cancer genetics is less understood compared to European American breast cancer susceptibility. Despite the many advantages of gene panel screening, studies investigating African American inherited breast cancer risk and comparing variant contributions between ethnicities are infrequent. Thus, 97 breast cancer-affected individuals of African and European descent from the Alabama Hereditary Cancer Cohort were screened using the research-based gene-panel, B.O.P. (Breast, Ovarian, and Prostate cancer). Upon sequencing and bioinformatic processing, rare coding variants in 14 cancer susceptibility genes were categorized according to the American College of Medical Genetics guidelines and compared between ethnicities. Overall, 107 different variants were identified, the majority of which were benign/likely benign. A pathogenic/likely pathogenic variant was detected in 8.6% and 6.5% of African American and European American cases, respectively, which was not statistically significant. However, African Americans were more likely to have at least one variant of uncertain significance (VUS; p-value 0.006); they also had significantly more VUSs in BRCA1/2 compared to European Americans (p-value 0.015). Additionally, 51.4% of African Americans and 32.3% of European Americans harbored multiple rare variants, and African Americans were more likely to have at least one VUS and one benign/likely benign variant (p-value 0.032), as well as multiple benign/likely benign variants (p-value 0.089). Moreover, of the 15 variants detected in multiple breast cancer cases, ATM c.2289T>C (p.F763L), a VUS, along with two likely benign variants, BRCA2 c.2926_2927delinsAT (p.S976I) and RAD51D c.251T>A (p.L84H), were determined to be associated with African American breast cancer risk when compared to ethnic-specific controls. Ultimately, B.O.P. screening provides essential insight towards the variant contributions in clinically relevant cancer susceptibility genes and differences between ethnicities, stressing the need for future research to elucidate inherited breast cancer risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / genetics*
  • Early Detection of Cancer / methods
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods
  • Genetic Variation / genetics*
  • Humans
  • Population Groups / genetics*

Grants and funding

This research was supported by the American Association of Colleges of Pharmacy (AACP) New Investigator Award, AU Research Initiative in Cancer (AURIC) Seed Grant, the Joy to Life Foundation Grant, and the AU Innovative Research grant through the Internal Grant Program with matching funds provided by AURIC and the Joy to Life Foundation (N.D.M). This research was also supported by the AURIC Graduate Fellowship Program (to M.R.B. and A.L. W.H.), the AU Cellular and Molecular Biosciences (CMB) Peaks of Excellence Research Fellowship (to M.R.B. and A.L.W.H.; NSF-EPS-1158862, grant G00006750), the Department of Drug Discovery and Development in the AU Harrison School of Pharmacy, the Department of Pathobiology in the AU College of Veterinary Medicine, and the AU College of Sciences and Mathematics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.