Genetic variability in 8q24 confers susceptibility to urothelial carcinoma of the upper urinary tract and is linked with patterns of disease aggressiveness at diagnosis

Abstract

Purpose: Upper urinary tract urothelial carcinoma is rare. Evidence shows that it behaves differently from urothelial bladder tumors. A polymorphism located at the T allele of rs9642880 on chromosome 8q24 is linked to an enhanced risk of bladder tumors. We explored the association of this polymorphism with susceptibility to upper urinary tract urothelial carcinoma.

Materials and methods: We genotyped the constitutional DNA of 261 patients with upper urinary tract urothelial carcinoma and 261 healthy controls matched for age, gender, smoking habit and ethnicity. Polymorphisms at rs9642880 on chromosome 8q24 were determined using the 5' nuclease polymerase chain reaction method with specific primers and probes. Frequencies were compared between cases and controls. Genotypes were in Hardy-Weinberg equilibrium for cases and controls.

Results: Mean patient age was 68.7 years. The T/T genotype resulted in a significantly higher risk of upper urinary tract urothelial carcinoma (OR 1.72, 95% CI 1.1-2.8, p = 0.028). Using single polytomous regression analysis the T/T genotype was also associated with aggressive tumors when stratified by stage (p = 0.003), or grade G2 (p = 0.04) or G3 (p = 0.01).

Conclusions: Our results strongly suggest that the T/T rs9642880 genotype is a risk factor for upper urinary tract urothelial carcinoma, as previously shown for bladder tumors. In contrast to bladder carcinoma, for upper urinary tract urothelial carcinoma the T/T genotype is associated with aggressiveness.