Inequities in multi-gene hereditary cancer testing: lower diagnostic yield and higher VUS rate in individuals who identify as Hispanic, African or Asian and Pacific Islander as compared to European

Abstract

The identification of germline pathogenic/likely pathogenic (P/LP) variants in cancer predisposition genes can guide treatment and management decisions for the individual being tested and potentially at-risk relatives. Prior studies have raised concerns of racial/ethnic disparities in the detection rates of P/LP variants and variants of uncertain significance (VUSs). In 2018, Color Genomics™, a commercial laboratory, made de-identified, aggregate genetic and clinical information from 50,000 individuals who completed testing for 30 cancer predisposition genes publicly available. It is the largest publicly available database of its kind from a single laboratory. An analysis of individuals from this database with a negative personal history of cancer that identify as European (n = 31,920), Hispanic (n = 1700), African (n = 462) or Asian and Pacific Islander (n = 2602), demonstrated that the VUS rate in the hereditary breast and ovarian cancer syndrome and Lynch syndrome genes was higher for all non-European groups as compared to the European group; Hispanic (7.1% vs. 5.8%; p = 0.029), African (12.3% vs. 5.8%; p < 0.001), Asian and Pacific Islander (13.1% vs. 5.8%; p < 0.001). In the other cancer genes (OCGs), the P/LP rate was lower; Hispanic (5.1% vs. 7.6%; p < 0.001), African (2.4% vs. 7.6%; p < 0.001), and Asian and Pacific Islander (4.3% vs. 7.6%; p < 0.001). The VUS rate was also higher in the OCGs; Hispanic (16.2% vs. 12.2%; p < 0.001), African (21.6% vs. 12.2%; p < 0.001), Asian and Pacific Islander (24.4% vs. 12.2%; p < 0.001). Our study emphasizes the reality of disparities in the results of cancer genetic testing and highlights factors that propagate these inequities.

Keywords: BRCA1/2; Cancer genetic testing; Health disparities; Hereditary cancer.