A variety of industrial exposures have also been implicated as risk factors for developing bladder cancer, primarily aromatic amines present in the production of dyes and benzidine and its derivatives; combustion gases and soot from coal, possibly chlorinated aliphatic hydrocarbons; chlorination by-products in heated water; and certain aldehydes (e.g., acrolein used in chemical dyes and in the rubber and textile industries).
Occupations reported to be associated with an increased risk of bladder cancer include those that involve organic chemicals such as dry cleaners, paper manufacturers, rope and twine makers, and workers in apparel manufacturing.[14,15,16,17]
It is estimated that 5% to 15% of patients in the United States who eventually die from bladder cancer will have strong exposure histories to the above-named environmental factors (other than smoking).
The use of contaminated Chinese herbs is also reported to be a risk factor. The prime carcinogen in these herbs appears to be aristolochic acid (AA) extracted from species of Aristolochia. Because of the diversity of Chinese herbal regimens used in addition to AA, other unidentified phytotoxins may also play a role. The chronic nephropathy associated with ingestion of herbs contaminated with A. fangchi has been linked to urothelial carcinoma of the renal pelvis and ureter. Herbs with A. fangchi are banned from Belgium, Canada, Australia, and Germany but are still available in the United States.
Ingestion of large quantities of arsenic in well water has also been associated with numerous malignancies, including TCC of the bladder.[22,23] Similar endemic pockets of bladder cancer are found in other regions with high arsenic concentrations in drinking water. In South Taiwan, arsenic blackfoot disease is endemic.
Additional risk factors associated with more aggressive forms of bladder cancer include prolonged exposures to urinary foreign bodies and infections; neuropathic bladder and associated indwelling catheters;[25,26]Schistosoma haematobium bladder infections (Bilharzial bladder cancer); exposure to the cancer chemotherapy agent cyclophosphamide [28,29,30,31] and perhaps other alkylating agents, such as ifosfamide (although the use of mesna in conjunction with these agents may reduce the incidence); and pelvic radiation therapy for other malignancies.[33,34,35] Renal transplant recipients appear to have an increased incidence of bladder cancer.
Urothelial tumors other than TCC include adenocarcinoma, squamous cell carcinoma, and metastatic adenocarcinoma. Risks for squamous cell tumors in the bladder include indwelling catheters [37,38] and S. haematobium cystitis.
Adenocarcinomas account for less than 2% of primary bladder cancers, including metastases from the rectum, stomach, endometrium, breast, prostate, and ovary.
Although occasional familial clusters have been anecdotally reported [39,40,41] and bladder cancer (as well as upper urinary tract TCC) is part of the Lynch family cancer syndrome II, there is no evidence that tendencies towards developing bladder cancer are inherited.