JCO Precision Oncology: Disparate Rates of Germline Variants in Cancer Predisposition Genes in African American/Black Compared With Non-Hispanic White Individuals Between 2015 and 2022 (Tomlinson)

Rachel B. Wyatt Castillo, MS, CGC, Sarah M. Nielsen, MS, CGC, Elaine Chen, PhDBrandie 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 ATMBRCA1BRCA2PALB2, and PMS2 were significantly higher in AA/B compared with NHW individuals, whereas rates of PGV in BRCA1BRCA2 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.

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