Disparate Rates of Germline Variants in Cancer Predisposition Genes in African American/Black Compared With Non-Hispanic White Individuals Between 2015 and 2022.

Abstract

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. 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 <i>P</i> < .05 was considered statistically significant. 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% <i>v</i> 32%; <i>P</i> < .0001) and lower (9% <i>v</i> 13%; <i>P</i> < .0001) in AA/B compared with NHW individuals. Rates of VUS in <i>ATM</i>, <i>BRCA1</i>, <i>BRCA2</i>, <i>PALB2</i>, and <i>PMS2</i> were significantly higher in AA/B compared with NHW individuals, whereas rates of PGV in <i>BRCA1</i>, <i>BRCA2</i>, and <i>PALB2</i> were higher in AA/B compared with NHW individuals (<i>P</i> < .001). Despite reductions in VUS frequencies over time, disparities in definitive GGT results persist. Increasing inclusion of AA/B populations in both testing and research will further increase knowledge of genetic variants across these racial groups.