Genetic and Epidemiological Features of Upper Tract Urothelial Carcinomas

The aim of this article is to describe the natural history and peculiarities of carcinogenesis of upper tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed on the Medline database (PubMed) using different combinations of the following key words: upper tract urothelial carcinoma, clonality, carcinogenesis, mutation, chromosomal instability, Lynch syndrome, and genetic polymorphism. Local development of UTUC is characterized by a highly prevalent multifocality that might be explained by the overlap of "field change" and "intra-luminal seeding and implantation" theories. UTUC and bladder tumors share common carcinogenesis mechanisms, such as mutations of FGFR3 and TP53, defining two distinct pathways of pathogenesis. The estimated UTUC incidence is 1.2 cases/100,000 inhabitants per year in Europe. The incidence of renal pelvis tumor has been stable for 30 years, while the frequency of ureteral locations has increased over time. Locally advanced stage and high grade are more frequent factors at the time of diagnosis. The median age for diagnosis is 70 years. Male-to-female ratio is nearly 2. Main carcinogenic factors are tobacco consumption and occupational exposure. There are specific risk factors for UTUC, such as Aristolochic acid (Balkan nephropathy and Chinese herbes nephropathy). Furthermore, specific genetic risk factors for UTUC includes Lynch syndrome, and different polymorphisms might explain an individual's susceptibility for developing these tumors.