MOLECULAR AND GENETIC EVENTS IN SCHISTOSOMIASIS-ASSOCIATED HUMAN BLADDER-CANCER - ROLE OF ONCOGENES AND TUMOR-SUPPRESSOR GENES

Carcinoma of the urinary bladder is the most common malignancy in many tropical and subtropical countries and is mainly due to endemic schis tosomal infection. Schistosomiasis-associated bladder cancer defines a characteristic pathology and cellular and molecular biology that diff ers from urothelial carcinoma of non-schistosomal origin. N-Nitroso co mpounds are suspected etiologic agents in the process of bladder cance r induction during schistosomiasis. Elevated levels of DNA alkylation damage have been detected in schistosome-infected bladders and are acc ompanied by an inefficient capacity of DNA repair mechanisms. Conseque ntly, high frequency of G-->A transition mutations were observed in th e H-ras gene and at the CpG sequences of the p53 tumor suppressor gene . Genetic changes have also been detected in the c-erbB-1 and c-erbB-2 oncogenes and in the cdkn2 and Rb tumor suppressor genes. The potenti al application of these mutational patterns in providing a biological marker suitable for the biomonitoring and early detection of this neop lasm could indicate new avenues of approach that might alleviate the p roblem in the future. It can also assist in elucidating the mechanisms by which schistosomiasis augments human bladder cancers.