Occupation is also a significant etiological factor, comprising 5-15% of UTUC with high risk professions including dry cleaning and metal industries. UTUC can also be caused by hereditary factors. The most common hereditary cause of UTUC is Lynch syndrome. It was first described in 1895, causes 1-5% of all cases of colorectal carcinomas, although 30-40% of Lynch syndrome tumors are not related to colon. Approximately 13% of Lynch syndrome tumors are UTUC. Lynch syndrome in general entails an 8-16 increase in relative risk for UTUC, without any increased risk for bladder cancer. The involved mechanism is mismatch repair gene mutations and microsatellite instability (MSI). Hereditary MSI occurs in 1-5% of patients, while acquired MSI occurs in 10% of patients, and this may affect prognosis and treatment sensitivity.
Another important cause for UTUC is diet. Chinese herb nephropathies are characterized by proximal tubular damage, renal interstitial fibrosis, slow progression to renal failure, and high prevalence of UTUC. It was found to be caused by the compound Aristolochic acid, which was found in the herbs and is highly associated with UTUC. Another similar nephropathy is the Balkans endemic nephropathy. Highest exposure to this nephropathy was found around the tributaries of the Danube River. There is known familial clustering but no Mendelian inheritance. This suggests environmental exposure with some genetic predisposition. The Relative risk of UTUC in these areas had decreased over the years from 57.1 to 11.2.
Presented by: James Catto
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre.Twitter: @GoldbergHanan at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal