A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor for skin cancer. But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And some people who get the disease may not have had any known risk factors. Even if a person with kidney cancer has a risk factor, it is often very hard to know how much that risk factor contributed to the cancer.
Genetic and hereditary risk factors
Some people inherit a tendency to develop certain types of cancer. The DNA that you inherit from your parents may have certain changes that give you this tendency to develop cancer. Some rare inherited conditions can cause kidney cancer. It is important that people who have hereditary causes of renal cell cancer see their doctors frequently, particularly if they have already had a renal cell cancer diagnosed. Some doctors recommend regular imaging tests (such as CT scans) for these people. People who have the conditions listed here have a much higher risk for getting kidney cancer, although they account for only a small portion of cases overall:
- Birt-Hogg-Dube (BHD) syndrome
BHD syndrome is characterised by an increased risk of a number of different types of renal cancer. People with this syndrome develop many small benign skin tumors and have an increased risk of developing different kinds of kidney tumors, including renal cell cancers and oncocytomas. They may also have benign or malignant tumors of several other tissues. The gene linked to BHD is known as folliculin (FLCN).
People with this syndrome develop tumors called paragangliomas of the head and neck region, as well as tumors known as pheochromocytomas of the adrenal glands and other areas. They also tend to get kidney cancer in both kidneys before age 40. It is caused by defects in the genes SDHB and SDHD (succinate dehydrogenase subunit B and D, respectively). These gene defects can also cause something called Cowden-like syndrome. People with this syndrome have a high risk of breast, thyroid and kidney cancers.
- Hereditary leiomyoma-renal cell carcinoma (HLRCC)
Individuals with HLRCC develop benign skin and uterine leiomyomas and, in some cases, highly aggressive type-2 papillary RCC. People with this syndrome develop smooth muscle tumors called leiomyomas (fibroids) of the skin and uterus (in women) and have a higher risk for developing papillary renal cell cancers. It has been linked to changes in the fumarate hydratase (FH) gene.
- Hereditary papillary renal cell carcinoma (HPRCC)
HPRCC is characterised by occurrence of type 1 papillary RCC as well as tumours in other organs. People with this condition have inherited a tendency to develop one or more papillary renal cell carcinomas, but they do not have tumors in other parts of the body, as is the case with the other inherited conditions listed here. This disorder is linked to changes in many genes, most often the MET gene.
- Hereditary renal oncocytoma
Some people inherit the tendency to develop a kidney tumor called oncocytoma, which has a very low potential for being malignant.
- Von Hippel-Lindau disease
The risk of someone with von Hippel Lindau disease developing clear-cell RCC increases with age, reaching 70% by age 60. People with this condition often develop several kinds of tumors and cysts (fluid-filled sacs) in different parts of the body. They have an increased risk for developing clear cell renal cell carcinoma, especially at a younger age. They may also have benign tumors in their eyes, brain, spinal cord, pancreas and other organs; and a type of adrenal gland tumor called pheochromocytoma. This condition is caused by mutations (changes) in the VHL gene.
Lifestyle-related and job-related risk factors
Obesity is an established risk factor for kidney cancer in both men and women. Risk increases by 24% in men and 34% in women for every additional 5 points in body mass index (BMI). A study published in December 2011 estimated that about 25% of kidney cancer cases in men and 22% in women in the UK in 2010 were linked to being overweight. The mechanisms proposed to explain the strong association with excess bodyweight include raised levels of insulin, oestrogens and growth factors, and changes in cholesterol metabolism or the immune system.
According to the Million Women Study, risk of kidney cancer increases by 29% per 10cm increase in height. Previous evidence for a relationship of height and kidney cancer risk was inconsistent.
People who are very overweight have a higher risk of developing renal cell cancer. Some doctors think obesity is a factor in about 2 out of 10 people who get this cancer. Obesity may cause changes in certain hormones that can lead to renal cell carcinoma.
Smoking increases the risk of developing renal cell carcinoma. The increased risk seems to be related to how much you smoke. The risk drops if you stop smoking, but it takes many years to get to the risk level of someone who never smoked.
The International Agency for Research on Cancer (IARC) states that kidney, renal pelvis and ureter cancers are all caused by tobacco smoking. On average, current smokers have a 50% increase in risk of kidney cancer. Risk increases with the number of cigarettes smoked per day. People who smoke more than 20 cigarettes per day increase their risk by 60-100% compared to people who have never smoked.
Kidney cancer risk declines after smoking cessation. As a group, former smokers have a 25% higher risk of kidney cancer. Those who quit ten or more years previously have a similar risk to lifelong never-smokers. Risk for cancer of the renal pelvis is increased by more than three-fold in current smokers and even higher risk increases have been shown for cancers of the ureter.
IARC states that there is limited evidence that exposure to arsenic and cadmium or printing processes can cause kidney cancer. Although trichloroethylene has been the subject of a number of studies in relation to kidney cancer, and the most recent meta-analysis showed around a 40% risk increase for occupational exposure, IARC does not classify trichloroethylene to be a risk factor for kidney cancer.
Many studies have suggested that workplace exposure to certain substances increases the risk for renal cell carcinoma. Some of these substances are asbestos, cadmium (a type of metal), some herbicides, benzene, and organic solvents, particularly trichloroethylene.
Other risk factors
People with advanced kidney disease, especially those needing dialysis, have a higher risk of renal cell carcinoma. Dialysis is a treatment used to remove toxins from your body if the kidneys do not work properly.
Diuretics: Some studies have suggested that diuretics (water pills) may be linked to a small increase in the risk of renal cell carcinoma. It is not clear whether the cause is the drugs or the high blood pressure they treat. If you need diuretics, you should take them. You shouldn't avoid them to try to reduce the risk of kidney cancer.
Phenacetin, once a popular non-prescription pain reliever, has been linked to renal cell cancer in the past. Because this medicine has not been available in the United States for over 20 years, this no longer appears to be a major risk factor.
- Family history of kidney cancer
The syndromes described above are rare, and it is thought that most of the familial risk for kidney cancer is not linked to them, but rather to more common genes with a smaller impact on risk. A meta-analysis reported a doubling in risk of renal cell carcinoma in people with a first-degree relative diagnosed with kidney cancer. The risk was approximately four times higher when the affected first-degree relative was a sibling. A family history of prostate cancer in a parent or sibling, or melanoma, non-Hodgkin lymphoma, bladder or thyroid cancer in a sibling has also been linked to an increased risk
People with a strong family history of renal cell cancer (without one of the known inherited conditions listed previously) also have a 2 to 4 times higher chance of developing this cancer. This risk is highest in brothers or sisters of those with the cancer. It's not clear whether this is due to shared genes or something that both people were exposed to in the environment − or both.
Renal cell carcinoma is about twice as common in men as in women. Men are more likely to be smokers and are more likely to be exposed to cancer-causing chemicals at work, which may account for some of the difference.
- High blood pressure (Hypertension)
The risk of kidney cancer is higher in people with high blood pressure. Some studies have suggested that certain medicines used to treat high blood pressure may raise the risk of kidney cancer, but it is hard to tell if it's the condition or the medicine (or both) that may be the cause of the increased risk.
The kidneys play a vital role in controlling blood pressure by regulating extracellular fluid (the fluid in the body lying outside the cells). When arterial pressure is high, the kidneys increase the rate at which both water and sodium are excreted. This in turn, results in less extracellular fluid and a decrease in blood pressure.
According to a meta-analysis, kidney cancer risk increases by around 60% in those with a history of hypertension (high blood pressure). There is a trend of increasing risk with progressively higher diastolic and systolic blood pressure. Risk of kidney cancer falls if hypertension is reduced.
Analyses excluding kidney cancer cases diagnosed within the first few years of follow-up for hypertension also show an increased risk of kidney cancer, arguing against the theory that the risk increase is a result of kidney cancers being more likely to be detected in those with hypertension, or that raised blood pressure is a result of early stage kidney cancer. Hypertension may cause damage to the kidney directly, or increase susceptibility to carcinogens. A US study estimated that 24% of renal cell carcinoma cases in women and 15% in men are linked to hypertension.
Some studies have shown an increased risk with use of diuretics and other anti-hypertensive medication, although it is not possible to say whether the effects are independent of hypertension. Recent evidence mainly indicates that anti-hypertensive medication does not increase kidney cancer risk once the hypertension is brought under control.
African Americans have a slightly higher rate of renal cell cancer. The reasons for this are not clear.
- Reproductive and intra-uterine factors
There is evidence of an increased risk of kidney cancer with increasing number of births. While some early studies pointed to confounding by BMI as an explanation for this association, recent evidence supports an increased risk with higher number of births after adjustment for BMI (75% risk increase for four children compared with one-two). There is some evidence for an increased risk after hysterectomy. It has been hypothesised that this is due to changes in the ureter following the procedure.46 However, not all studies showing an association adjusted for BMI, and a recent cohort study that included this factor in the analysis did not show an association. One cohort study showed no association with either number of births or hysterectomy, and more research is needed in this area.
Factors shown to have no effect on kidney cancer risk
The World Cancer Research Fund in its 2007 report Food, Nutrition, Physical Activity and the Prevention of Cancer stated that the evidence indicates that alcohol does not have a substantial adverse effect on kidney cancer risk, and that evidence was inadequate to be able to say whether it has a protective effect. There is a 27% risk reduction for alcohol drinking, according to a recent meta-analysis. Almost all this benefit is conferred by light-moderate drinking (up to 15g/day), with no further risk reduction above this level. However, alcohol consumption is known to increase risk of several other cancer types, including breast and bowel.
Aspirin use was not been linked to risk in a meta-analysis, and more than one subsequent study. Paracetamol has also not been linked to risk in more than one study.
Individuals infected with hepatitis C have been shown to be at no increased risk of RCC in a large recent study, and IARC does not classify hepatitis C infection as a cause of kidney cancer. However, one previous study did report an association.
