Pathogenic germline variants among patients with ovarian cancer by self-reported ancestry: A commercial laboratory...

Ovarian cancer (OC) is highly lethal, and ∼15-20 % of cases occur in patients with germline pathogenic variants (gPVs) in BRCA1/2 and other genes related to homologous recombination (HR) and mismatch repair. We sought to characterize the germline landscape of patients with OC by self-identified ancestry.

Patients with epithelial OC who received germline testing were identified from the publicly available Myriad Collaborative Research Registry. Rates of gPVs were calculated, overall and by self-reported ancestry, with a focus on HR-related and Lynch syndrome (LS)-associated genes.

Among 84,396 patients with OC, 55,984 (66.3 %) identified as White, 6099 (7.2 %) as Hispanic, 4440 as Black (5.3 %), 3628 (4.3 %) as Ashkenazi Jewish (AJ), 2900 (3.4 %) as Asian, and 19,706 (23.3 %) as Other. Overall, 13,554 (16.1 %) patients had a gPV, with highest rates among AJ (24.4 %), followed by Hispanic (18.8 %), Asian (17.4 %), and White (15.6 %) patients, p < 0.0001. Most gPVs were in HR genes, specifically BRCA1/2, and occurred in 11,661 (13.8 %) patients with significant differences by ancestry, p < 0.001. The highest gPV rates in HR- related genes were in those of AJ ancestry (23.7 %) with similar rates in Hispanic (16.8 %), Asian (15.6 %), Black (14.9 %), and White (13.1 %) populations. Lynch syndrome gPVs were found in 778 (0.92 %) patients with highest rates in Asians (1.3 %).

Among >84,000 patients with OC, 16.1 % had a gPV, supporting recommendations for universal germline testing. Although those of AJ ancestry had the highest prevalence of gPV, Hispanic and Asian patients also had high gPV rates, supporting inclusive testing strategies given universal recommendations.