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 schistosomal infection. Schistosomiasis-associated bladder cancer defines a characteristic pathology and cellular and molecular biology that differs from urothelial carcinoma of non-schistosomal origin. N-Nitroso compounds are suspected etiologic agents in the process of bladder cancer induction during schistosomiasis. Elevated levels of DNA alkylation damage have been detected in schistosome-infected bladders and are accompanied by an inefficient capacity of DNA repair mechanisms. Consequently, high frequency of G --> A transition mutations were observed in the 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 potential application of these mutational patterns in providing a biological marker suitable for the biomonitoring and early detection of this neoplasm could indicate new avenues of approach that might alleviate the problem in the future. It can also assist in elucidating the mechanisms by which schistosomiasis augments human bladder cancers.