The Role of Molecular Mechanisms in the Development of Bladder Carcinoma: Review

Abstract

Studies performed in Western countries has proven that the bladder carcinoma, which occupies an important place among all cancers, constitutes 5-10% of all male cancers and is the fourth most common cancer in males, while it is eighth most common cancer in females and constitutes 4% of all female cancers. Although etiology of bladder carcinoma is not clearly known, environmental, demographic and genetic factors are thought to be influential. The environmental factors that play role in the development of bladder carcinoma are smoking, occupational carcinogens, schistosomiasis, chronic cystitis, administration of cyclophosphamide for therapeutic purposes and pelvic radiotherapy. Demographic factors that play a role in the development of bladder carcinoma are gender, race and age. The mutations on the different levels of tumor suppressor genes and oncogenes have an important role in the development of bladder carcinomas. Oncogenes have dominant effects on cellular levels i.e when they are activated or their expression levels are increased, even a single mutant allel may be sufficient to convert a cell from normal phenotype to malignant phenotype. Well known oncogens that are related to bladder carcinoma are H-ras, erb-B2 and c-myc. On the contrary, tumor suppressor genes are inhibitors of cell proliferation. To be influential in the development of bladder carcinoma, both allelles of tumor supressor genes must lose their functions so that these genes are recessive in respect to their effects in the development of bladder carcinoma. The retinoblastoma gene (Rb) on chromosome 13q and p 53 gene on chromosome 17p are the most widely studied tumor suppressor genes. Abnormalities on angiogenesis, extracelllular matrix and adhesion molecules are effective in progression of cancer. In addition, microsatellite instability as well as various epigenetic factors are also shown to be effective in the progression and development of bladder carcinoma. Further studies are required for enlightening the complicated mechanisms of the development and the progression of bladder carcinoma.