What Causes Kidney Cancer?

Cancer is caused by changes in the DNA inside our cells. DNA carries our genetic information (genes), which controls how our cells function. Our DNA, which comes from both our parents, affects more than just how we look.

Changes (mutations) in genes

Some genes normally help control when our cells grow, divide to make new cells, or repair mistakes in DNA, or they 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.

Changes in several genes are usually needed to cause kidney cancer. These changes can either be inherited from a parent, or they can be acquired during a person’s lifetime.

Inherited gene mutations 

Certain inherited gene changes can run in some families and increase the risk of kidney cancer. The inherited syndromes these changes cause lead to a small portion of all kidney cancers, and are described in Risk Factors for Kidney Cancer.

For example, the VHL gene is a tumor suppressor gene. It normally helps keep cells from growing out of control. Mutations (changes) in this gene can be inherited from parents, leading to von Hippel-Lindau (VHL) disease. When the VHL gene is mutated, it is no longer able to control the abnormal growth, and kidney cancer is more likely to develop.

Inherited changes in the following tumor suppressor genes also lead to an increased risk of kidney cancer:

• The FH genes (linked to hereditary leiomyomas which can cause fibroids in the skin and uterus)
• The FLCN gene (as seen in Birt-Hogg-Dube syndrome)
• The SDHA, SDHB, SDHC, and SDHD genes (as seen in the paraganglioma-pheochromocytoma syndromes)

People with hereditary papillary renal carcinoma have inherited changes in the MET oncogene that cause it to be turned on all the time. This can lead to uncontrolled cell growth and make a person more likely to develop papillary RCC. 

Special genetic tests can detect some of the gene mutations linked with these inherited syndromes. If you have a family history of kidney cancer or other cancers linked to these syndromes, you may want to ask your doctor about genetic counseling and genetic testing.

Genetic testing can be complex. Before having it done, it’s important to speak with a qualified cancer genetics professional. They can explain how testing might help you, how it is done, its limitations, and what the results might mean. For more on this, see Gene Changes and Cancer.

Acquired gene mutations

Some gene mutations happen during a person’s lifetime and are not passed on. They affect only cells that come from the original mutated cell. These changes are called acquired mutations. In most people with kidney cancer, the gene mutations that lead to cancer are acquired rather than having been inherited.

Certain risk factors, such as exposure to cancer-causing chemicals, might play a role in causing some of these acquired mutations. For example, when people  smoke, the lungs absorb many of the cancer-causing chemicals in tobacco smoke into the bloodstream. Because the kidneys filter this blood, many of these chemicals become concentrated in the kidneys. Several of these chemicals are known to damage kidney cells in ways that can cause the cells to become cancer.

Excess body weight, another risk factor for kidney cancer, alters the balance of some of the body’s hormones. Researchers are now learning how certain hormones help control the growth (both normal and abnormal) of many different tissues in the body, including the kidneys.

However, many of the acquired gene changes that can lead to kidney cancer can be just random events that sometimes happen inside a cell, without having an outside cause.

Most people with non-inherited clear cell RCC have changes in the VHL tumor suppressor gene in their cancer cells that have caused the gene to stop working properly. These gene changes are acquired during a person's life.

Other gene changes may also cause renal cell carcinomas. Researchers continue to look for these changes. For more about how genes changes can lead to cancer, see Gene Changes and Cancer .