Abstract: TH-OR029
Genetic Architecture of Renal Cell Cancer (RCC) in the Million Veteran Program Highlights Differences by Ancestry and Papillary Subtype
Session Information
- Genetics of Complex Kidney Traits
November 06, 2025 | Location: Room 360A, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits
Authors
- Mamak, Fatih, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Wang, Guanchao, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Chen, Hua-Chang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Triozzi, Jefferson Lorenzo, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Hung, Adriana, VA Tennessee Valley Healthcare System, Nashville, Tennessee, United States
Group or Team Name
- KidPhenGen Vanderbilt Precision Nephrology Program.
Background
Kidney cancer is among the top 10 cancers in the US, affecting more than 600,000 people. RCC is more common in African Americans and men. People with advanced kidney disease have a 5-fold increased risk of RCC.
Methods
GWASs of RCC and of papillary renal cell carcinoma (PRCC), stratified by genetic ancestry were completed. Controls included European ancestry (EUR) 448,131; African ancestry (AFR) 120,446 and Admixed American (AMR) 59,942 individuals.; RCC cases included EUR 4115, AFR 1422, and AMR 596 cases. GWASs were adjusted for age, sex and 10 principal components of ancestry.
Results
The mean age was 61 years (SD 15) for cases and 65 years (SD 10) controls. Ancestry was: 69% EUR, 18% AFR and 9% AMR. There were 10 independent loci associated with RCC overall for EUR. The strongest association was with MYEOV (rs7939454; p-value 9.92E-14), followed by SSPN/ITPR2 (rs4963975; p: 8.74E-10) and MAD1L1 (rs1801368; p: 2.01E-09). There were 9 independent loci associated with PRCC in EUR. The strongest association was with MYEOV (rs10908258;p:1.17E-11), five loci were in CKD genes (IL6R, IGFBP3, SHROOM3, TRPC7, SLC5AA48). VHL was associated with RCC (rs3087462; p:1.85E-16) and PRCC (rs7629500; p: 8.98E-08) only in AFR . Most loci in cancer genes were known. Novel loci in 5 genes are reported-not replicated yet: ANKL2, IRAK2, GYPB, PTPN13, SNX16 (Table 1).
Conclusion
Our study supports important differences in the genetic architecture of RCC by ancestry, including in the contributions of VHL to the risk of RCC and PRCC, only observed for AFR in this study. Longitudinal studies evaluating the value of these markers in prognosis and recurrence risk are needed. Also for the association CKD and PRCC.
Table 1. Genetic variants associated with RCC and PRCC in EUR & AFR
Funding
- Veterans Affairs Support