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.