Detection Rate and Spectrum of Pathogenic Variations in a Cohort of 83 Patients with Suspected Hereditary Risk of Kidney Cancer

Hereditary predisposition to cancer affects about 3–5% of renal cancers. Testing criteria have been proposed in France for genetic testing of non-syndromic renal cancer. Our study explores the detection rates associated with our testing criteria. Using a comprehensive gene panel including 8 genes related to renal cancer and 50 genes related to hereditary predisposition to other cancers, we evaluated the detection rate of pathogenic variants in a cohort of 83 patients with suspected renal cancer predisposition. The detection rate was 7.2% for the renal cancer genes, which was 2.41-fold higher than the estimated 3% proportion of unselected kidney cases with inherited risk. Pathogenic variants in renal cancer genes were observed in 44.5% of syndromic cases, and in 2.7% of non-syndromic cases. Incidental findings were observed in CHEK2, MSH2, MUTYH and WRN. CHEK2 was associated with renal cancer (OR at 7.14; 95% CI 1.74–29.6; p < 0.003) in our study in comparison to the gnomAD control population. The detection rate in renal cancer genes was low in non-syndromic cases. Additional causal mechanisms are probably involved, and further research is required to find them. A study of the management of renal cancer risk for CHEK2 pathogenic variant carriers is needed.