Carcinoma of the bladder accounts for 4 % of all cancers (with an incidence in men of 30 per 100,000 and in women of 10 per 100,000 in the UK), is the fifth most common cancer in men, and has a peak prevalence in the seventh decade. Environmental factors, including tobacco, amine compounds used in the manufacture of dyes, and schistosomiasis, have been clearly implicated in bladder Tumoursigenesis, but genetic factors may also be relevant. Ninety percent of bladder Tumours are transitional cell carcinomas, which may contain elements of squamous carcinoma or adenocarcinoma. Less commonly, sarcoma, melanoma, or small cell undifferentiated carcinoma may occur.
Familial clusters of bladder cancer were reported by Fraumeni and Thomas (1967) and McCullough et al. (1975). In these reports, bladder cancer affected a total of ten individuals from two-generation families. Lynch et al. (1979) also described two families showing a predisposition to transitional cell carcinoma of the bladder and renal pelvis. One individual developed bladder cancer at the age of 24 years. Familial clustering of bladder cancer could reflect shared exposure to environmental hazards or genetic susceptibility. A role for genetic factors is indicated by the association of bladder and other urothelial cancers with Lynch (HNPCC) syndrome and by the increased risk of bladder cancer in patients with germline RB1 mutations. However, the most important contribution of genetic factors to bladder cancer risk is probably in determining individual susceptibility to environmental carcinogens, such as tobacco or occupational exposure to aromatic amine compounds. Hence, research into genetic susceptibility to bladder cancer has focused predominantly on the identification low-penetrance susceptibility genes, and large numbers of SNPs that convey small increases in relative risks have been identified. These SNPs are linked to genes implicated in detoxification of carcinogens, control of the cell cycle, and apoptosis and maintenance of DNA integrity (Golka et al. 2011).
Bladder Tumours are frequently synchronous or metachronous. However, while these features are classical indicators of genetic susceptibility, molecular studies have suggested that multicentricity does not reflect a high incidence of multiple primary Tumours but rather than a single primary transformation event may seed other Tumours by spread across the urothelium.
Individuals who are at increased risk of bladder cancer should be screened by 6-monthly urinalysis and urinary cytology, with cystourethroscopy when these tests are abnormal. Analysis of urine sediment for microsatellite DNA markers may provide a novel method for monitoring bladder cancer recurrence (Steiner et al. 1997).