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 someone's chance of developing the disease.

Kidney cancer is more common in men, in those who smoke or are obese, those who have been exposed to certain chemicals at work, and those who have medical conditions such as high blood pressure. Kidney cancer risk is also higher in people who have a family history of the disease or who have inherited certain genetic syndromes.

The incidence of kidney cancer has been increasing in recent years, though we don't seem to know why. Some researchers believe this isn't a true increase, but rather an increased ability to find and diagnose the disease due to imaging tests such as CT scans and MRI scans.

If you learn that you are at increased risk, you may feel overwhelmed. Remember, having elevated risk does not guarantee that you'll develop the cancer, and there are still some factors that are in your control. Speak to your healthcare professional about any lifestyle changes you can implement like managing your weight, exercise, and healthy eating, and be aware of common symptoms so that you can follow up as needed.

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

We have, however, found several risk factors for the disease. Risk factors may increase the chance that a person will develop cancer kidney cancer, but do not necessarily cause the cancer. It's also important to note that people can and do develop kidney cancer even though they don't have any risk factors for the disease.

Some of the known risk factors for kidney cancer include the following.

Age

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

Sex

Kidney cancer is roughly twice as common in men as in women.

Race

The risk of kidney cancer is slightly higher in blacks than in whites.

Geography

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

Smoking

Smoking is a clear risk factor for kidney cancer, and those who smoke are 50 percent more likely to develop the disease. Smoking is thought to be responsible for 30 percent of kidney cancers in men and 25 percent in women.

The risk is related to the number of pack-years smoked, or the number of cigarettes smoked daily multiplied by the number of years a person smoked. Like the case with lung cancer, the risk of kidney cancer decreases when a person quits smoking but 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, and 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, there are people living today who may have used the medication, so it is important to talk to your doctor about any medical problems you have had in the past. It appears that Phenacetin is a very significant risk factor for development of the disease. One study found that the incidence of kidney cancer (in the renal pelvis) in Australia dropped by 52 percent in women and 39 percent in men over the 30 year period after it was banned in that country in 1979.

There is some concern that nonsteroidal anti-inflammatory drugs such as Advil (ibuprofen) may increase the risk. A link has also been found between the use of aspirin and Tylenol (acetominophen) and kidney cancer. These risks are thought to be primarily due to the overuse of these pain medications but is an important reason to use these preparations only when absolutely necessary.

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 the development of kidney cancer include:

• High blood pressure: As noted above, it's not certain whether high blood pressure is a risk factor for kidney cancer, or rather the medications used to treat the condition.
• History of lymphomas: It's uncertain whether lymphomas themselves predispose a person to kidney cancer, whether both cancers share an underlying gene mutation, or whether radiation used to treat lymphomas is responsible for the increased risk.
• 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 immunspression increases the risk.
• History of thyroid cancer: People who have had thyroid cancer appear to be two to seven times more likely to develop kidney cancer. It's not certain if thyroid cancer (or its treatment) plays a direct role, or rather if a gene mutation such as those in tumor suppressor genes contributes to the risk of both cancers.
• Diabetes: The risk of kidney cancer is slightly higher in people with diabetes, particularly those who have been treated with insulin.

Chemical Exposures

Most exposures to substances and chemical 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 and a concern for gas station workers), and some herbicides (used in farming).

Reproductive Factors

Results from more than one study seem to indicate that women who have a hysterectomy have a significantly increased risk of developing kidney cancer (around 28 percent in one and 41 percent in another). In contrast, the risk of kidney cancer is lower in women who have their first period (menarche) at a later age, and those who have used the birth control pill (oral contraceptives).

Most people who develop kidney cancer do not have a family history of the disease, but having a family history of kidney cancer increases your risk. Having a first degree relative with the disease (parent, sibling, or child) doubles the risk, but 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) have the disease, and especially for those who have a family member who was diagnosed before the age of 50 or had more than one kidney cancer.

If more than one family member has been diagnosed with kidney cancer, or if family members have been diagnosed at a young age, there is a possibility that one of the genetic syndromes below could run in your family. At the current time, however, gene testing is in its infancy. Further genetic syndromes and gene mutations will likely be discovered in the future.

In addition to family history, people with some genetic syndromes have an elevated risk. These syndromes are currently thought to account for 5 percent to 8 percent of kidney cancers, and include:

• Von Hippel-Lindau syndrome: People with this syndrome have a very high risk of clear cell renal carcinoma (around 40 percent of people 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