Environmental and Genetic Factors Contributing to Bladder Carcinogenesis

The carcinogenesis of bladder cancer is a complex interplay between genetic and environmental factors. The urinary bladder has significant exposure to many mutagenic environmental substances as these are excreted in the urine. Mutagenic substances can be ingested or inhaled, with inhalation of cigarette smoke likely responsible for the majority of environmental bladder cancer risk. Routes of environmental carcinogenesis other than the urine include infection, inflammation, radiation, and immunosuppression. Advances in molecular sequencing have characterized a number of polymorphisms associated with various cancer-related mechanisms to predispose to bladder cancer. Germline predisposition as part of characterized pathogenic mutations in cancer-associated genes (e.g., BRCA1/2 and MMR-deficiency) is also an increasingly recognized mechanism of bladder cancer carcinogenesis.