Risk Factors and Molecular Features Associated with Bladder Cancer Development

Bladder cancer remains a global epidemiologic problem, with a strong male predominance and association with tobacco smoking. However, several other risk factors have also been associated with development of this disease, which is characterized by alterations in multiple molecular pathways. Development of the more prevalent, less aggressive, recurrent, noninvasive tumors is characterized by constitutive activation of the Ras–MAPK pathway. The less common but more aggressive invasive tumors, which have a higher mortality rate, are characterized by alterations in the p53 and retinoblastoma pathways. Alterations in pathways involved in cell-cycle regulation, apoptosis, cell signaling, angiogenesis, and tumor cell invasion have been shown to influence disease behavior. Combined assessment of these alterations can contribute valuable information that can accurately predict outcome and therapeutic response in individual patients with bladder cancer. Risk-stratifying patients based on exposure and molecular profiles will ultimately allow implementation of rational therapeutic strategies for optimal disease management.