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Description of the Evidence

    continued...

    Among the chemicals implicated in smoking-induced bladder cancer are aminobiphenyl and its metabolites.[7] It is possible that inherited and inducible enzymes are important in the activation and detoxification of aminobiphenyls and other putative bladder carcinogens. These enzymes include N-acetyltransferase 2 (NAT2),[8] cytochrome P450 1A2 (CYT 1A2),[9] and glutathione S-transferase M 1.[10] Several studies have indicated that specific genotypes and phenotypes of these enzymes and their activities, particularly in the liver and urothelium, are associated with susceptibility to smoking-induced bladder cancer and bladder cancer induced by other aryl amines, particularly in industrially exposed populations.[8,9,10,11,12,13] Not all of these studies, however, have been well controlled for active or former smoking histories.

    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;[14] combustion gases and soot from coal, possibly chlorinated aliphatic hydrocarbons;[15] chlorination by-products in heated water;[16] and certain aldehydes (e.g., acrolein used in chemical dyes and in the rubber and textile industries).[17]

    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).[18]

    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.[19] Because of the diversity of Chinese herbal regimens used in addition to AA, other unidentified phytotoxins may also play a role.[20] 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.[21]

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