Epidemiology and Etiology of Premalignant and Malignant Urothelial Changes

Abstract

Bladder neoplasms are common around the world. Incidences are particularly high in the Nile River Valley secondary to schistosomiasis, which is frequently associated with the development of squamous cell carcinoma similar to that of other chronic inflammatory processes of the lower urinary tract. However, elsewhere, most bladder tumors are of the urothelial (transitional) cell type. There is a marked male predominance and there are extensive racial differences. It is predominantly a neoplasm that occurs in patients aged >50 years. Urothelial carcinomas comprise two distinct diseases both biologically and molecularly: a low-grade papillary tumor which frequently recurs; and a high-grade malignancy which can present as dysplasia or carcinoma in situ, but frequently presents as invasive disease. However, epidemiological investigations of urothelial malignancies have generally not distinguished between preneoplastic and invasive neoplasms or between these two types of urothelial neoplasms. It is recommended that future studies should distinguish between these entities. The most common etiologic factor of urothelial malignancies besides schistosomiasis is cigarette smoking. In addition, numerous specific chemicals have been identified as bladder carcinogens in humans, some relating to specific occupational exposures. Bladder carcinogens include aromatic amines and amides, such as 4-aminobiphenyl, benzidine, 2-naphthylamine and phenacetin-containing analgesics, and certain cancer chemotherapeutic agents, such as phosphoramide mustards. More recently, occupational exposure to various combustion gases, such as diesel exhaust, has been related to an increased risk of developing bladder neoplasms. Also, exposure to chlorination by-products in drinking water and to arsenic has been suggested as increasing the risk of bladder neoplasia. As numerous specific chemicals appear to be related to the development of bladder tumors, various polymorphisms of enzymes involved in their metabolism have been suggested as affecting the susceptibility to their carcinogenicity. This has been particularly true with respect to the role of acetyltransferases in relation to aromatic amine carcinogenesis. Dietary influences have also been suggested as affecting bladder neoplasia susceptibility. Various heterocyclic amines generated by pyrolysis of food have been suggested as potential dietary factors increasing the risk of bladder cancer, particularly in relation to the ingestion of red meat. Despite the existence of several identifiable factors that increase or decrease the risk of bladder cancer, many patients have no known carcinogens or risk factors.