The Association of Uromodulin Genotype with Renal Cancer Aggressiveness

The aim of the study was to investigate the association of the uromodulin (UMOD) genotype with patient health status and with renal cell carcinoma (RCC) aggressiveness.The UMOD genotype at the top single nucleotide variant rs4293393 was determined in a cohort of 211 patients diagnosed with a renal mass and treated with surgery. Clinical data were prospectively collected. Due to the higher frequency of allele T relative to the lower frequency of allele C, recessive homozygous (CC), and heterozygous (TC) patients were grouped together and compared with homozygous (TT) patients. Mann-Whitney and chi-square tests were used to compare clinical characteristics after stratification for the UMOD genotype. UMOD genotype frequencies resulted TT and TC-CC in 67% (n = 141) and 33% (n = 70) of the population, respectively. The rate of cM1 RCC at clinical staging was higher in patients with genotype TT relative to patients with genotype TC-CC (18% vs 1%, p = 0.001). Similarly, the rate of pT3-pT4 (41% vs 25%, p = 0.047) and lymphovascular invasion (29% vs 13%, p = 0.02) RCC at final pathology were higher in patients with genotype TT relative to patients with genotype TC-CC. Patient summary: In patients diagnosed with renal cell carcinoma and treated with surgery, uromodulin homozygous genotype is associated with more aggressive renal cell carcinoma clinical and pathological characteristics. In patients diagnosed with a renal mass and elected for surgical management, uromodulin homozygous genotype is associated with more aggressive renal cell carcinoma clinical and pathological characteristics. Further investigations are required to study the causal biologic mechanism underlying such relationship.