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Researchers don’t know exactly what causes most bladder cancers. But they have found some risk factors (see Bladder Cancer Risk Factors ) and are starting to understand how some of them might cause cells in the bladder to become cancer.

How DNA changes (mutations) can cause cancer

Certain changes in the DNA inside normal bladder cells can make them grow out of control. DNA is the chemical in our cells that makes up our genes, which control how our cells function. We usually look like our parents because they are the source of our DNA, but our genes affect more than just how we look.

Some genes normally help control when our cells grow, divide to make new cells, repair mistakes in DNA, or cause cells to die when they’re supposed to. If these genes aren’t working properly, it can lead to cells growing out of control. For example:

• Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control and forming a tumor. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

DNA changes can either be acquired during a person’s lifetime, or they can be inherited from a parent.

Acquired gene mutations

Most gene mutations related to bladder cancer develop during a person’s life, rather than having been inherited from a parent.

Sometimes these acquired gene mutations might be the result of exposure to cancer-causing chemicals or radiation. For example, chemicals in tobacco smoke (and other substances) can be absorbed into the blood, filtered by the kidneys, and end up in urine, where they can affect bladder cells.

On the other hand, some gene changes may just be random events that sometimes happen inside a cell, without having an outside cause.

The gene changes that lead to bladder cancer are not the same in all people. Acquired changes in certain genes, such as the TP53 or RB1 tumor suppressor genes and the FGFR3, PIK3CA, and HRAS oncogenes, are thought to be important in the development of some bladder cancers. Changes in these and similar genes may also make some bladder cancers more likely to grow and spread than others.

Inherited gene mutations

Some people inherit gene changes from their parents that increase their risk of bladder cancer (see Bladder Cancer Risk Factors). But bladder cancer does not often run in families, and inherited gene mutations are not thought to be a major cause of this disease.

Some people inherit changes in genes (such as GSTM1 and NAT2) that lower their ability to detoxify (break down) and get rid of certain types of cancer-causing chemicals. These people are more sensitive to the cancer-causing effects of tobacco smoke and certain industrial chemicals. Researchers have developed tests to identify such people, but these tests are not routinely done. It’s not certain how helpful the results of such tests might be, since doctors already recommend that all people avoid tobacco smoke and hazardous industrial chemicals.