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Homologous recombination deficiency in ovarian high-grade serous carcinoma by self-reported race

Katherine A Lawson-Michod1,2, Courtney E Johnson3, Mollie E Barnard1,2,4

  • 1Huntsman Cancer Institute, Salt Lake City, UT, USA.

Medrxiv : the Preprint Server for Health Sciences
|February 20, 2025
PubMed

Insights

Homologous recombination deficiency (HRD) in ovarian cancer differs by race. Black individuals had more variants of uncertain significance (VUS) and a higher prevalence of HRD signatures and BRCA2 variants, impacting survival analysis.

Area of Science:

  • Genomics
  • Oncology
  • Population Health

Background:

  • Homologous recombination deficiency (HRD) is common in ovarian high-grade serous carcinomas (HGSC), affecting approximately 50% of cases.
  • HRD is not well-characterized across different racial groups, particularly in Black individuals.
  • Understanding racial disparities in HRD is crucial for equitable precision medicine.

Purpose of the Study:

  • To characterize HGSC HRD features by self-reported race.
  • To evaluate associations between racial differences in HRD and ovarian cancer mortality.
  • To investigate the impact of variants of uncertain significance (VUS) on HRD assessment in diverse populations.

Main Methods:

  • A cohort study utilizing data from two population-based case-control studies of ovarian cancer.
  • Inclusion of 178 Black and 123 White individuals with pathologically confirmed HGSC.
  • Identification of HRD features via whole-exome DNA sequencing, including germline/somatic variants and mutational signatures.

Main Results:

  • Black individuals had a higher prevalence of HRD signatures (40% vs. 29%) and germline BRCA2 variants (8% vs. 2%) compared to White individuals.
  • A greater proportion of detected variants were unannotated or VUS in Black individuals (germline 65% vs. 45%; somatic 62% vs. 50%).
  • Among Black individuals, BRCA2 variants were linked to better survival, while BRCA1 variants were associated with worse survival.

Conclusions:

  • HRD testing is vital for precision medicine in ovarian cancer.
  • A higher VUS proportion in Black individuals may hinder access to targeted therapies.
  • Increased diversity in genomics research and improved VUS characterization are essential for equitable cancer care.
Abstract

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