Rachel B. Wyatt Castillo, MS, CGC, Sarah M. Nielsen, MS, CGC, Elaine Chen, PhD, Brandie Heald, MS, CGC,, Rachel E. Ellsworth, PhD Edward D. Esplin, MD, PhD, FACMG, and Gail E. Tomlinson, MD, PhD
Abstract
Purpose
African American/Black (AA/B) individuals are under-represented in genomic databases and thus less likely to receive definitive information from germline genetic testing (GGT) than non-Hispanic White (NHW) individuals. With nearly 500,000 AA/B and NHW individuals having undergone multigene panel testing (MGPT) for hereditary cancer risk at a single commercial laboratory, to our knowledge, we present the largest study to date investigating cancer GGT results in AA/B and NHW individuals.
Methods
MGPT results from a retrospective cohort of AA/B (n = 48,684) and NHW (n = 444,831) patients were evaluated. Frequencies of pathogenic germline variants (PGVs) and variants of uncertain significance (VUS) were compared between AA/B and NHW individuals. Changes in frequency of VUS over time were determined. Pearson’s chi-squared test was used to compare categorical variables among groups. All significance tests were two-tailed, and P < .05 was considered statistically significant.
Results
Between 2015 and 2022, rates of VUS decreased 2.3-fold in AA/B and 1.8-fold in NHW individuals; however, frequencies of VUS and PGV remained significantly higher (46% v 32%; P < .0001) and lower (9% v 13%; P < .0001) in AA/B compared with NHW individuals. Rates of VUS in ATM, BRCA1, BRCA2, PALB2, and PMS2 were significantly higher in AA/B compared with NHW individuals, whereas rates of PGV in BRCA1, BRCA2 and PALB2 were higher in AA/B compared with NHW individuals (P < .001).
Conclusion
Despite reductions in VUS frequencies over time, disparities in definitive GGT results persist. Increasing the inclusion of AA/B populations in both testing and research will further increase knowledge of genetic variants across these racial groups.