• Molecular biology and genetics of bladder cancer
• Risk Factors

Despite the ongoing research in the molecular and genetic etiologies of bladder cancer, no single defect or marker has been identified. Rather, various genes, proteins and enzymes have been studied intensively since it has been discovered that they do play an essential role in both the transformation of normal cells to tumor cells, and the progression of non-invasive tumors to invasive and metastatic ones. The following will briefly describe some of the more well-studied concepts in molecular and genetic oncology as it relates to bladder cancer. It is important to note that most of these concepts have not been applied to general medical practice.

1) Oncogenes: Recall that genes are specially ordered molecules of DNA from which a given cell can synthesize proteins. Any disarrangement of these molecules is called a mutation. Many genes in a given cell are "turned off" since they are not necessary in that cell's daily function. For example, a replication gene may encode a protein that enables a cell to divide. If this gene is not "turned off" or regulated appropriately, perhaps as a result of a mutation, the cell may divide incessantly, possibly resulting in a tumor. In this case, the gene is designated as an oncogene because it has this capacity of malignant transformation. To clarify, it is a gene whose protein product has a normal function in causing cells to divide, but when out of control can result in tumorigenesis. Several oncogenes have been identified in bladder cancer cells. The ras gene codes for a protein known as p21 and has been found in approximately 10% of bladder tumors.¹ The c-myc oncogene has been identified in superficial bladder tumors that have a greater tendency to recur and progress to invasive disease.² Finally, a gene known as c-jun codes for a protein known as a transcription factor.³ These proteins are literally the "on-off" switches for the replication gene exemplified above. A mutation in the c-jun gene might lead to the inability of this so-called switch to be in the "on" position, resulting in uncontrolled cell replication.

2) Tumor Suppressor Genes: These genes encode proteins which work to control or regulate cell growth and replication. A mutation in a tumor suppressor gene will take the "off" switch out of the process of cell division, leading to uncontrolled replication. Two important and well-studied tumor supressor genes are known as the "retinoblastoma tumor supressor gene"(Rb) and the "p53 tumor supressor gene". Regarding the former, despite its name, this gene and its encoded protein, pRb, is found in many types of tumors, not the least of which are bladder tumors. The P53 gene encodes the protein of the same name. To restate, these proteins work by stopping a cell from dividing. For example, when a mutation occurs within a cell's DNA, levels of p53 within that cell will rise to effectively halt that cell from further replication. All tumor cells have damaged DNA, and it is likely that p53 or a protein like it is either abnormally absent or malfunctioning such that the cell continues to divide out of control. Both the p53 and pRb proteins are thought by some to play important roles in determining prognosis and survival in bladder cancer.⁴

3) Growth Factors: Cells use these chemicals to communicate with one another throughout the body. If a tissue is damaged, the surrounding cells may react by releasing growth factors into the blood stream or even locally within their own tissue. These complex molecules will attach to the receptor of a nearby cell and cause a series of reactions within it, which in this case might lead to cell division to replace the once that were damaged. Scientists have noticed that certain growth factors are in higher concentration either within tumors or in the urine of patients with bladder tumors. Examples of these factors are epidermal growth factor(EGF), fibroblast growth factor(FGF), and transforming growth factor(TGF). Despite the ability of these growth factors to cause bladder cancer cells to grow in the laboratory, their detection in humans has not demonstrated any profound effect on prognosis or survival.