What causes renal transitional cell carcinoma?

Updated: Nov 05, 2019
  • Author: Bagi RP Jana, MD, MBA, MHA, FACP; Chief Editor: E Jason Abel, MD  more...
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The exact cause of upper urinary tract TCC is not known; however, several risk factors have been identified.

Workers in the chemical, petrochemical, aniline dye, and plastics industries, as well as those exposed to coal, coke, tar, and asphalt, are at increased risk for renal pelvis and ureteral tumors.

Cigarette smoking appears to be the most significant acquired risk factor for upper urinary tract UC. It is suggested that 70% of upper urinary tract urothelial tumors in men and 40% of those in women can be attributed to smoking.

Two chronic tubulointerstitial disorders, Balkan endemic nephropathy and Chinese herbs nephropathy, are also risk factors for upper urinary tract urothelial tumors. Both have been linked to exposure to aristolochic acid. [2] Balkan endemic nephropathy is confined to regions located along the Danube River and its tributaries. It appears to result from dietary exposure to aristolochic acid in the seeds of Aristolochia clematitis (European birthwort), a native plant that may comingle with local wheat. [3] Chinese herbs nephropathy likely results from aristolochic acid found in certain herbal remedies used in traditional Chinese medicine. [2]

Analgesic abuse is a risk factor; a combination of phenacetin use and papillary necrosis results in a 20-fold increase in risk for renal urothelial tumors. Phenacetin was removed from the US market in 1983, and phenacetin-related upper urinary tract UC has become vanishingly rare. [4]

Chronic bacterial infection with urinary calculus and obstruction may predispose to the development of urothelial cancer. SCC is the most common entity in these cases. Schistosomiasis also may predispose to SCC.

The chemotherapy drugs cyclophosphamide and ifosfamide are implicated in the development of urothelial cancers in the upper and lower urinary tract, particularly after drug-induced hemorrhagic cystitis.

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