Ethnicity-Specific Variation in the Germline Landscape of Renal Cell Carcinoma

Prior studies of the germline landscape of renal cell carcinoma (RCC) have centered around predominantly white patients of European ancestry. We examined the frequency of germline pathogenic and likely pathogenic (P/LP) variants in 1,829 patients with RCC from various ancestries. Overall, P/LP variants were found in 17%, among which 10.3% harbored ≥1 clinically actionable germline variant with potential preventive or therapeutic utility. Patients with African ancestry harbored significantly more P/LP variants in FH compared to patients of European ancestry. Patients with European ancestry had significantly more P/LP variants in CHEK2 and overall had more actionable variants compared to patients with African ancestry. This work helps better understand the underlying biological differences in RCC between Africans and Europeans. In addition, this work may pave the way to a much more comprehensive and global genomic characterization of underrepresented populations.