Etiology, diagnostics, prevention and treatment of endemic nephropathy and associated urothelial cancer – importance of genome and proteome study

Balkan endemic nephropathy (BEN) is a chronic tubulointestitial disease described in some rural parts of South-East Europe. One of its most peculiar characteristics is a strong association with upper urothelial carcinomas (UUC). The etiology of BEN and associated UC is not yet fully understood but there appears to be a polygenic susceptibility to the disease involving interactions between multiple environmental factors and multiple genes.The main problems with UUC and bladder cancer are detection, recurrence, and progression. Identification of biomarkers may improve the screening and diagnosis of urothelial cancer (UC), characterize the malignant potential, and determine the prognosis. Microarray-based gene-expression profiling enables the rapid, simultaneous measurement of gene expression on a genome-wide scale.The application of state of the art genetic screening technologies for genomic and proteomic analyses will contribute to discover previously nondescribed molecular alterations in urothelial cancers associated with BEN and in sporadic UC. It is therefore expected that the proposed project would lead to the elucidation of specific and common underlying mechanisms involved in predisposition to BEN and UC. Markers that distinguish among UC, normal urothelium, and benign urothelial conditions are potential diagnostic, prognostic, and therapeutic targets.