The mutational signatures and molecular alterations of bladder cancer

Bladder cancer is the ninth most common cancer in the world, 430,000 new cases and 165,000 deaths each year around the world (1). The incidence is four times higher in men than in women; therefore, it is the seventh most common cancer in men and the seventeenth in women (2). The distribution of this type of cancer around the world differs (2). The highest incidences of bladder cancer are in Northern America and Europe (highest in Belgium, 17.5 cases per 100,000; age-standardized rate), while the lowest are in Asia, Latin America and Caribbean (i.e., 5.2 cases per 100,000 in South Korea). In Western countries, >90% of bladder cancers are transitional cell carcinoma (TCC) (urothelial carcinoma). However, in some developing countries, ~75% of cases are squamous cell carcinoma (3). These differences are presumably due to different carcinogenic exposures in different countries. Tobacco smoking and occupational exposures to aromatic amines and polycyclic hydrocarbons are the major risk factors in Western countries (4,5). However, in other countries, other environmental factors, i.e. schistosomiasis infections (Africa and the Middle East, i.e., Egypt), drinking water containing arsenic (Southeast Taiwan) and, presumably, aristolochic acid are responsible for cases of bladder cancer (6-8)