Environmental Risk Factors
About 30% of RCC in men and about 25% in women may be due directly to smoking. Smoking doubles the risk of developing RCC.
Some studies suggest that work exposure to asbestos increases the risk of RCC.
Some studies suggest that work exposure to cadmium may increase RCC risk. Cadmium may also increase the cancer-causing effect of smoking.
Genetic and Hereditary Risk Factors
Inherited and acquired gene mutations
Human cells contain 23 pairs of chromosomes. Each of these chromosomes contains many genes that are made of DNA. The genes that we inherit from our parents make us who we are. Genes are the reason that we often have a similar appearance to our parents. In addition to determining how we look, genes also control every aspect of our body's metabolism. This is why abnormal genes can cause some diseases. Abnormalities of genes are called mutations. Gene mutations that cause some diseases (such as sickle cell disease) can be inherited. Recently, researchers have found gene mutations that cause some rare syndromes such as tuberous sclerosis and Von Hippel- Lindau. People with these mutations have an increased risk of developing of kidney tumors.
Some other mutations involved in formation of kidney cancers that are not inherited are also known. Most risk factors for cancer somehow damage the DNA that forms genes. For example, cigarette smoke is a risk factor for kidney cancer and many other cancers. Cigarette smoke contains chemicals that damage genes of kidney cells which may help predispose to cancer formation.
A family history of kidney carcinoma
Some patients with RCC may have inherited one or more genes that increase their risk for this disease. The exact function of these genes and how they cause RCC are not completely known. This hereditary form of RCC usually occurs in both kidneys and causes multiple tumors appear. Hereditary forms of RCC have been found involving both clear cell and papillary cell type RCC although the specific mutations causing these tumors are different.
Von Hippel-Lindau syndrome (VHL)
This disease is characterized by multiple tumors of the kidneys, brain, spine, eyes, adrenal glands, pancreas, inner ear, or epididymis. Von Hippel-Lindau disease occurs in about 1 in 36,000 births and tends to occur in clusters within families. VHL patients have high incidence of developing clear cell RCC and the cancers usually develop at an early age. About 40% of people with this disease have either cysts or tumors in both kidneys. Some can have many small RCCs throughout their kidneys. The gene that causes von Hippel-Lindau disease has been found and is called the VHL gene. It is located on chromosome 3. Tests looking for the VHL gene mutation are becoming available. It also has been shown that high number of sporadic clear cell RCC show genetic alterations involving VHL gene thus underscoring importance of this gene in pathogenesis of clear cell RCC.
This disease is characterized by numerous bumps on the skin (caused by small tumors of the blood vessels), seizures, mental retardation, and cysts in the kidneys, liver and pancreas. Patients with this disease also have an increased risk of developing RCC.
Other Risk Factors
Diet and weight
Some studies find a greater risk of RCC in people who are overweight and those who eat a high-fat diet.
Long-term kidney failure
Some patients with chronic (long-term) kidney failure who are treated with dialysis over a long period of time may develop cysts in their kidneys. RCCs may develop from the cells that line these cysts. For this reason, many doctors recommend periodic ultrasound examinations or CT scans for these patients, so that any kidney cancers that develop are likely to be found at an early stage, when their prognosis will be most favorable.
Most RCCs occur in adults between the ages of 50–70 years. They are rare in children and young adults.
RCC is twice as common in men than in women.