What Causes Kidney Cancer?

Although many risk factors can increase the chance of developing renal cell cancer (RCC), it is not yet clear how some of these risk factors cause kidney cells to become cancer.

Changes (mutations) in genes

Cancer is caused by changes in the DNA inside our cells. DNA is the chemical in our cells that makes up our genes. Genes control how our cells function. DNA, which comes from both our parents, affects more than just how we look.

Some genes help control when our cells grow, divide into new cells, and die:

• Certain genes that help cells grow, divide, and stay alive are called oncogenes.
• Genes that help keep cell division under control or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes, resulting in cells growing out of control. Changes in many different genes are usually needed to cause kidney cancer.

Inherited gene mutations

Certain inherited DNA changes can run in some families and increase the risk of kidney cancer. These syndromes, which cause a small portion of all kidney cancers, are described in Risk Factors for Kidney Cancer.

For example, VHL, the gene that causes von Hippel-Lindau (VHL) disease, 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. 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 SDHB and SDHD genes (as seen in familial renal cancer)

People with hereditary papillary renal cell 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 makes the person more likely to develop papillary RCC.

Special genetic tests can detect some of the gene mutations associated 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. The American Cancer Society recommends discussing genetic testing with a qualified cancer genetics professional before any genetic testing is done. For more on this, see Understanding Genetic Testing for Cancer and What Happens during Genetic Testing for 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 DNA changes are called acquired mutations.

In most cases of kidney cancer, the DNA mutations that lead to cancer are acquired during a person’s life rather than having been inherited. Certain risk factors, such as exposure to cancer-causing chemicals (like those found in tobacco smoke), probably play a role in causing these acquired mutations, but so far it’s not known what causes most of them. Progress has been made in understanding how tobacco increases the risk for developing kidney cancer. Your lungs absorb many of the cancer-causing chemicals in tobacco smoke into the bloodstream. Because your 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.

Obesity, another risk factor for this 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.

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

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 Genetics and Cancer.