Racial and ethnic variation in BRCA1 and BRCA2 genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center

Cancer Causes Control. 2023 Feb;34(2):141-149. doi: 10.1007/s10552-022-01648-w. Epub 2022 Nov 12.


Purpose: The prevalence of pathogenic variants in BRCA1 and BRCA2 in populations other than Ashkenazi Jewish (AJ) is not well defined. We describe the racial and ethnic-specific prevalence of BRCA1/2 pathogenic variants and variants of uncertain significance (VUS) among individuals referred for genetic testing in a large urban comprehensive cancer center over a 20-year period.

Methods: The population included 3,537 unrelated individuals who underwent genetic testing from January 1999 to October 2019 at the Karmanos Cancer Institute. We estimated the prevalence of pathogenic variants and VUS and evaluated associations with race and ethnicity for African American (AA), Arab, AJ and Hispanic individuals compared to Non-Hispanic Whites (NHW). We used multivariable models to adjust for other predictors of pathogenic variants. We also reported the most common pathogenic variants by racial and ethnic group.

Results: The racial and ethnic breakdown of our population was: NHW (68.9%), AA (20.3%), AJ (2.5%), Arab (2.2%), Hispanic (1.0%), Asian Pacific Islander, Native American/Alaskan Native (4.7%), and < 1% unknown. The overall prevalence of pathogenic variants in BRCA1/2 was 8.9% and the prevalence of VUS was 5.6%. Compared to NHW, there were no racial or ethnic differences in the rate of pathogenic variants. However, AA individuals were more likely to have VUS in BRCA1 (adjusted OR 2.43, 95% CI 1.38-4.28) and AJ were more likely to have VUS in BRCA2 (adjusted OR 3.50, 95% CI 1.61-6.58).

Conclusion: These results suggest the continued need for genetic testing and variant reclassification for individuals of all racial and ethnic groups.

Keywords: BRCA1; BRCA2; Breast cancer; Ethnicity; Race.

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein* / genetics
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / genetics
  • Ethnicity / genetics
  • Female
  • Genetic Counseling*
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Genetic Variation
  • Hispanic or Latino / genetics
  • Humans


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human