title: Urothelial carcinoma associated with Balkan endemic nephropathy. A worldwide disease.
abstract: Balkan endemic nephropathy (BEN), a familial chronic tubulo-interstitial disease with a slow progression to terminal renal failure, affects people living in the alluvial plains along the tributaries of the Danube River. One of its most peculiar characteristics is a strong association with upper urothelial cancer. An increased incidence of upper urinary tract (UUT) transitional cell cancer (TCC) was discovered among the inhabitants of endemic settlements and in families affected by BEN. In areas where BEN is endemic, the incidence of upper tract TCC is significantly higher, even 100 times, than in non-endemic regions. A high incidence of urothelial cancer in end-stage BEN patients strongly suggests preventive nephro-ureterectomy in all end-stage patients with BEN treated with either transplantation or dialysis. Better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression, has provided a large number of molecular markers of TCC, with a potential diagnostic and prognostic value. Markers that distinguish among TCC, normal urothelium, and benign urothelial conditions are potentially diagnostic, prognostic, and therapeutic targets. The geographic correlation and presence of AA-DNA adducts in both BEN and associated urothelial cancer, support the speculation that these diseases share a common etiology. Dietary exposure to AA is a significant risk factor for BEN and its attendant transitional cell cancer. These are cases of well-known AA induced urothelial carcinoma, and could be detected worldwide. The presence of more than one risk factors is possible and it is important to test etiological hypotheses in different endemic foci, preferably as a multicentric research.
authors.affiliation: Faculty of Medicine, Institute of Nephrology, Bul. Zorana Djindjica 81, 18000 Nis, Serbia. stefan@ni.ac.yu
authors.forename: V
authors.initials: V
authors.lastname: Stefanovic
authors.forename: M
authors.initials: M
authors.lastname: Polenakovic
authors.forename: D
authors.initials: D
authors.lastname: Toncheva
mesh_terms: D034341:Aristolochic Acids / Q000009:adverse effects; D001449:Balkan Nephropathy / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D002295:Carcinoma, Transitional Cell / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology; D018736:DNA Adducts; D004032:Diet; D019353:Endemic Diseases; D006801:Humans; D011379:Prognosis; D012307:Risk Factors; D014571:Urologic Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D034341:Aristolochic Acids; D018736:DNA Adducts; C000228:aristolochic acid I