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 since the 1990s, though it seems to have leveled off in the past few years. This was likely due to newer imaging tests, such as CT scans, that increased the ability to find and diagnose 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 the cancer, and there are still some factors that are in your control.

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 kidney cancer, but do not necessarily cause the cancer.

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

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.

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

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

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

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.

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.

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.

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.

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 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.
• Radiation therapy for another cancer: Women who have had radiation for cervical cancer, or men who had radiation for testicular cancer, have an elevated risk.
• HIV/AIDS: Immunosuppression alone is a risk factor for kidney cancer, but the medications used to treat HIV appear to 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 often lacks symptoms until it has done significant damage.
• Kidney stones: Kidney stones may be a risk factor in men, but this association has not been seen in women.

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).

Results from more than one study seem to indicate that women who have a hysterectomy have a significantly increased risk of developing kidney cancer (approximately 30 percent to 40 percent). 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