Do we know what causes kidney cancer?

Although many risk factors may increase the chance of developing kidney cancer, it is not yet known exactly how some of these risk factors cause kidney cells to become cancerous.

Changes (mutations) in genes

Researchers are beginning to understand how certain changes in DNA can cause normal kidney cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes − the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look.

Some genes control when our cells grow, divide, and die. Certain genes that speed up cell division and stop cells from dying when they are supposed to are called oncogenes. Others that slow down cell division, 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.

Inherited gene mutations

Certain inherited DNA changes can lead to conditions running in some families that increase the risk of kidney cancer. These syndromes, which cause a small portion of all kidney cancers, were described in the section, "What are the 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, causing von Hippel-Lindau disease. When the VHL gene is mutated, it is no longer able to suppress abnormal growth, and kidney cancer is more likely to develop. The genes linked to hereditary leiomyoma and renal cell carcinoma (the FH gene), Birt-Hogg-Dube syndrome (the FLCN gene), and familial renal cancer (SDHB and SDHD) are also tumor suppressor genes, and inherited changes in these genes also lead to an increased risk of kidney 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 renal cell cancer.

Acquired gene mutations

Most DNA mutations related to kidney cancer, however, occur during a person's life rather than having been inherited. These acquired changes in oncogenes and/or tumor suppressor genes may result from factors such as exposure to cancer-causing chemicals (like those found in tobacco smoke), but in many cases what causes these changes is not known.

About 3 out of 4 people with sporadic (non-inherited) clear cell renal cancer have changes in the VHL gene that cause it not to function properly. These changes were acquired during life rather than being inherited.

Other gene changes may also cause renal cell carcinomas. Researchers continue to look for these changes.

Progress has been made in understanding how tobacco increases the risk for developing renal cell carcinoma. 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 highly concentrated in the kidneys. Several of these chemicals are known to damage kidney cell DNA in ways that can cause the cells to become cancerous.

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.

What is known about the gene changes that lead to kidney cancer is being used to help develop new treatments for this disease. For example, researchers now know that the VHL gene normally stops cells from making a substance called vascular endothelial growth factor (VEGF). Tumors need new blood vessels to survive and grow and VEGF causes new blood vessels to form. Newer drugs that target VEGF are now being used to treat kidney cancer. They are described in the section, “Targeted therapies for kidney cancer.”