Causes and Risk Factors for Kidney Cancer

We don't know the exact causes of kidney cancer, but there are several risk factors that increase the chance of developing the disease.

Kidney cancer is more common in males, smokers, and people who are obese, have been exposed to certain chemicals at work, or have medical conditions such as high blood pressure. Your risk of kidney cancer is also higher if you have a family history of the disease or if you've inherited certain genetic syndromes.

The incidence of kidney cancer has been increasing since the 1990s, though it has leveled off in the past few years. According to the American Cancer Society, the increase in diagnosis was likely due to newer imaging tests, such as CT scans, that improved the ability to identify and stage the disease.

If you learn that you are at increased risk, you may feel overwhelmed. Remember, having elevated risk does not guarantee that you'll develop cancer, and there are still some factors that are in your control.

Lifestyle Risk Factors

The exact causes of kidney cancer have not been identified, but we know that this type of cancer usually begins when a series of genetic mutations in a normal kidney cell transforms it into a cancer cell.

There are several risk factors that may increase the chance of developing kidney cancer, but they do not necessarily cause the cancer to occur.

Age

The risk of kidney cancer increases with age, though these cancers have been found in people of all ages, even children. The disease is diagnosed most commonly between the ages of 50 and 70.

Sex

Kidney cancer is roughly twice as common in males as in females.

Race

The risk of kidney cancer is slightly higher in Blacks than Whites.

Geography

Kidney cancers are more common among those who live in urban areas than in rural areas.

Smoking

Smoking is a clear risk factor for kidney cancer, and people who smoke are 50% more likely to develop the disease. Smoking is thought to be responsible for 30% of kidney cancers in males and 25% of kidney cancers in females.

The risk of kidney cancer decreases when a person quits smoking, but it can remain elevated for a long time. The risk finally drops to that of a never-smoker around 10 years after quitting.

Obesity

People who are overweight or obese (have a body mass index greater than 30) are more likely to develop kidney cancer. In fact, obesity is thought to be responsible for 1 out of 4 kidney cancers. Obesity leads to changes in hormone levels in the body that could be related to this risk.

Medications

There are some medications that are clearly associated with kidney cancer, and others where we still aren't certain whether there is a risk.

One class of pain medications has long been linked with kidney cancer. Phenacetin, a painkiller that was once widely used, was banned in the United States in 1983 due to this concern. That said, if you've used this medication in the past, it's important to tell your healthcare provider about it.

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It appears that Phenacetin is a very significant risk factor for the development of the disease. One study found that the incidence of kidney cancer in Australia dropped by 52% in females and 39% in males over the 30 year period after the medication was banned in that country in 1979.

Diuretics or "water pills" (specifically, hydrochlorothiazide) may also be associated with an increased risk of kidney cancer. At the current time, it's not certain whether the risk is related to the use of these drugs to treat high blood pressure or due to the presence of high blood pressure itself.

Medical Conditions

Medical conditions that have been associated with kidney cancer include:

• High blood pressure
• Immunosuppression: A suppressed immune system, whether due to drugs for organ transplants, inherited immune disorders, acquired diseases such as HIV/AIDS, or other forms of immunosuppression increases the risk of most types of cancer.
• Diabetes: The risk of kidney cancer is slightly higher in people with diabetes, particularly those who have been treated with insulin.
• Radiation therapy for another cancer: Females who have had radiation for cervical cancer or males who had radiation for testicular cancer have an elevated risk.
• HIV/AIDS: Immunosuppression alone is a risk factor for kidney cancer, and the medications used to treat HIV may increase risk as well.
• Advanced kidney disease: People with advanced-stage kidney disease, particularly those who are on dialysis, have an increased risk.
• Chronic hepatitis C infection: Recently, hepatitis C has also been found to increase the risk of kidney cancer. It's now recommended that anyone born between 1945 and 1965 have a blood test to screen for hepatitis C, as the disease usually doesn't cause symptoms until it has done significant damage.
• Kidney stones: Kidney stones may be a risk factor in males, but this association has not been seen in females.

Chemical Exposures

Most exposures to substances and chemicals that raise risk are related to on-the-job (occupational) exposures.

Some of these include exposure to:

• Trichloroethylene, an organic solvent used to strip paint from metals
• Perchloroethylene, used in dry cleaning and metal degreasing
• Cadmium, found in cadmium batteries
• Asbestos, found in older construction
• Benzene, found in gasoline
• Some herbicides, used in farming

Reproductive Factors

Results from more than one study indicate that after a hysterectomy, females have a significantly increased risk of developing kidney cancer (approximately 30 to 40%). In contrast, the risk of kidney cancer is lower in females who have their first period (menarche) at a later age, and those who have used the birth control pill (oral contraceptives).

Genetics

Most people who develop kidney cancer do not have a family history of the disease, but having a family history of this cancer increases the risk.

Having a first-degree relative with the disease (parent, sibling, or child) doubles the risk, and the risk is higher if a sibling has the disease (suggesting an environmental component as well).

The risk of kidney cancer is also higher when more than one relative (even extended relatives) has the disease, especially if the family member was diagnosed before the age of 50 or had more than one kidney cancer.

If you have more than one family member who has been diagnosed with kidney cancer, or if you have family members who have been diagnosed at a young age, there is a possibility that one of the genetic syndromes that are associated with kidney cancer could run in your family.

These syndromes are currently thought to account for 5 to 8% of kidney cancers.

• Von Hippel-Lindau syndrome: People with this syndrome have a very high risk of clear cell renal carcinoma (around 40% develop the disease), due to a mutation in the VHL gene
• Hereditary papillary renal cell carcinoma
• Hereditary leiomyoma-renal cell-renal cell carcinoma
• Birt-Hogg-Dube syndrome
• Cowden syndrome
• Tuberous sclerosis
• It's possible that you or other family members may have a genetic syndrome that's associated with an elevated risk even if none of your family members have been diagnosed with kidney cancer.