Introduction

Renal cell carcinoma (RCC), often known as kidney cancer, was originally thought to be a single type of cancer. More recent research shows that it consists of different kinds of cancer with different genetic associations and with various therapies that work best.¹ What they all have in common is that they begin in the kidneys, the organs which remove waste from your blood and excrete it as urine. Kidneys are located below your ribs, above your waist. Possible symptoms include:²

• Blood in urine
• Sweating, especially at night 
• Feeling tired 
• Loss of appetite 
• Unintentional weight loss
• Pain/lump between ribs and waist

While anyone can develop kidney cancer, there are some risk factors which increase your chances:³

• Smoking 
• High blood pressure
• Overweight 
• A close relative has kidney cancer
• Long-term dialysis 
• Inherited conditions 

Understanding the risk factors in kidney cancer is important to allow people to minimise their risk and focus on preventing cancer. It also helps those at risk identify themselves so they can monitor symptoms, undergo screening, and seek medical advice. Early detection improves survival outcomes because cancer may be less advanced, and treatment can be started as soon as possible.³

Testing for kidney cancer will involve an appointment with your GP, followed by blood and urine tests and scans. An ultrasound scan can look at your kidneys from outside your body, while a cystoscopy may be carried out to investigate your bladder. A CT scan can look at your kidneys as well as other organs to find out if any cancer has spread. There may also be other tests and scans involved, as directed by a specialist doctor known as a urologist.²

Treatment for kidney cancer depends on the specific type of cancer, whether it has spread, and its exact location and size. When found in the early stages, surgery can remove the cancer or the whole kidney. If you are not well enough to have this surgery, there are other options, including radiofrequency ablation using a needle into your kidney. Chemotherapy is used less often for kidney cancer, but it is sometimes used for certain types.

Understanding kidney cancer risk factors

Modifiable risk factors

Modifiable risks are those that you can change, allowing you to lower your chances of developing cancer. 

Smoking

Smoking is a risk factor for several cancers, including kidney cancer. This is due to the presence of carcinogens in tobacco. The risk from smoking is higher when smoking for longer, and the risk begins to decrease after smoking is stopped. A good way to minimise your risk is to reduce or quit smoking.³

Obesity

Another risk factor associated with several cancers is obesity and a poor diet. This includes high-fat diets and a lack of physical activity. It is still not clear exactly how obesity increases the risk of kidney cancer, but some researchers have suggested it may be due to hormones. Physical activity has many beneficial effects, including lowering blood pressure, reducing obesity, and reducing insulin resistance. Increased physical activity, therefore, lowers your risk of kidney cancer.³

High blood pressure

Studies have found that a history of high blood pressure is associated with an estimated 67% increased risk of kidney cancer. The exact reason for this is still unclear, but it is thought that renal hypoxia is involved. This is where your kidneys do not get enough oxygen. When you have high blood pressure, your blood vessels are strained, which can make them narrow. When this happens around the kidneys, they do not get enough blood flow, meaning they do not get enough oxygen and nutrients that your blood carries. This means the kidneys cannot do their job as well. High blood pressure also causes transcription of factors which induce hypoxia, as well as promoting the proliferation of tumour cells.^3,4

Exposure to harmful substances

Exposure to harmful substances, particularly at work, has been suggested to have a link with kidney cancer. This includes pesticides and asbestos; however, research is often conflicting. This makes it difficult to say exactly to what extent, if any, environmental factors may be involved in the development of kidney cancer, and more research is needed.

Long-term use of certain pain medications

Some studies have found that in long-term use of some pain medications, such as acetaminophen, there is an increased risk of kidney cancer. The same results were found across geographical regions and gender. As with the other risk factors, the exact way these medications increase the risk of kidney cancer is unknown. However, it is suggested that long-term and excessive use leads to kidney damage, known as renal papillary necrosis, where kidney tissue dies. More research is needed to clarify these effects because many other studies state that pain medications can have a protective effect against other cancers.⁵

Non-modifiable risk factors

Family history and genetic conditions

Studies across several populations show that a family history of kidney cancer does not guarantee cancer, but it does increase the risk of developing kidney cancer. This could be explained by inherited conditions such as von Hippel-Lindau disease (VHL), which is caused by mutations in a gene known as VHL, a tumour suppressor, and it can lead to cancer development in organs, including the kidneys. This is the most common hereditary cause of kidney cancer. Another genetic mutation involved in kidney cancer is mutations in the BHD gene, known as Brit-Hogg-Dubé syndrome. These involve germline mutations in the folliculin gene, which is another tumour suppressor that regulates cell growth and metabolism.^6,7,8

Gender

Kidney cancer is twice as common in people assigned as male at birth as in people assigned as female at birth. This may be due to genes being expressed differently, regulating metabolism and other factors involved in cancer differently. While identification of these genes is a good starting point, more research is needed to understand the differences between genders when it comes to cancer. Understanding specific genes involved could allow for the development of more targeted therapies, which are likely to have better outcomes.⁹

Long-term dialysis

Patients with chronic kidney disease (CKD), especially those on dialysis for a long time, have an increased risk of developing kidney cancer. This does not necessarily fit into either modifiable or non-modifiable risk, because dialysis is a necessary medical intervention if your kidneys do not work well.¹⁰ 

CKD involves damage to your kidneys, meaning they cannot perform as well, allowing substances that can harm the kidneys further to build up. Additionally, patients who are on dialysis may have irritation of their kidneys, and the damage may allow toxins to build up in the blood. These are some proposed mechanisms for the increased risk, but it is not completely clear yet what causes the increase.¹⁰

Strategies for risk management 

Lifestyle changes to reduce risk

There are ways to reduce your risk of developing kidney cancer by targeting the modifiable risks discussed above. You can:^3,4

• Quit smoking, or cut down
• Lose weight/maintain a healthy weight
• Eat a balanced diet, lowering intake of fat
• Stay physically active
• Monitor blood pressure and seek medical advice

Medical strategies

Unfortunately, the steps above only target modifiable risks. It is much harder to manage non-modifiable risks, including genetic conditions and family history. However, there are still some steps you can take to monitor your risks and catch kidney cancer in the early stages, which will improve treatment outcomes. These steps include:¹⁰ 

• Attend regular health checkups with your GP
• If you are at high risk, you can seek genetic testing to identify any genetic condition you may carry and receive counselling on managing this 
• Monitor your health and kidney function, particularly if you already have another kidney disease and if you are on dialysis

Awareness and early detection

It is useful to be aware of the symptoms of kidney cancer so you can identify any concerns. If you do experience symptoms or any changes in your usual health, it is important to seek medical advice. The earlier you seek help, the earlier you can be diagnosed with kidney cancer. Early detection is important because it is associated with improved treatment outcomes and survival rates; because of this, screening is crucial. It is estimated that over 50% of cases of kidney cancer are found in people with no symptoms being investigated for other conditions.¹¹

Summary

It is important to note that not everyone who has these risk factors will develop kidney cancer. They only increase the chances of developing cancer. There are several ways to reduce the risk, which will also improve overall health and minimise the risk of other cancers and diseases. This includes the lifestyle changes discussed above, as well as monitoring health and being aware of symptoms so you can seek medical help. Taking control of your health today can shape a healthier tomorrow.