Environmental factors involved in carcinogenesis of urothelial cell carcinomas of the upper urinary tract

Primary cancers of the ureter and renal pelvis are rare tumours, > 90% of which are transitional cell carcinomas. Only approximately 5% of urothelial tumours arise in the upper urinary tract (UUT). Many environmental factors contribute to the development of these cancers. Some are similar to bladder cancer-associated factors (tobacco, occupational exposure), while others are more specific to carcinogenesis of the UUT (phenacetine, Balkan endemic nephropathy [BEN], Chinese herb nephropathy or association with Blackfoot disease [BFD]). This review discusses the environmental factors involved in UUT carcinoma. Tobacco and occupational exposure remain the principal exogenous risk factors for developing these tumours. Conversely, carcinogenesis of UUT tumours resulting from phenacetine consumption has almost disappeared. Although the incidence of BEN is also on the decline, roles for aristolochic acid and the consumption of Chinese herbs in the physiopathology and induction of this nephropathy, respectively, have proposed. In Taiwan, the association of this tumour type with BFD and arsenic exposure remains unclear to date. As some genetic polymorphisms are associated with an increased risk of cancer or faster disease progression, there is variability in interindividual susceptibility to the development of UUT carcinoma when exposed to the aforementioned risk factors Cytosolic sulfotransferases (SULTs) catalyse the detoxification of many environmental chemicals but also in the bioactivation of dietary and other mutagens. Polymorphism of the SULT gene, is thought to confer susceptibility to upper tract tumours.