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 cancerous.
Changes (mutations) in genes
Researchers are starting to understand how certain changes in the DNA inside normal kidney cells can cause them to become cancerous. DNA is the chemical 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 into new cells, and die. Certain genes that help cells grow, divide, and stay alive 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 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 “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. 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 (the SDHB and SDHD genes) 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 RCC.
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 often what causes these changes is not known. Many gene changes are probably just random events that sometimes happen inside a cell, without having an outside cause.
Most people with sporadic (non-inherited) clear cell RCC have changes in the VHL gene in their tumor cells that have caused it to stop working properly. These changes are 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 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 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.
Last Revised: 02/10/2016