Kidney Cancer: Risk Factors & Preventative Measures
By: Dhwani Patel, Ching Yung Yuan, Mackenzie Smith
The kidneys are important organs in our body that function to filter out waste and toxins from our blood by excreting them in the form of urine. Unfortunately, kidney cancer is a very severe disease affecting Canadians, with an estimated 8600 Canadians being diagnosed and 1900 Canadians dying from kidney and renal pelvis cancer in 2023 alone (1). There are various types of kidney cancer including urothelial carcinoma and sarcoma, however, the most common type of kidney cancer is renal cell carcinoma (RCC) (1). RCC affects the renal tubules of the kidney, which are especially important for filtering and cleaning the blood (1). RCC is very painful and can lead to symptoms such as blood in the urine, abdominal and back pain, fever, and constant tiredness. It can also result in death if untreated (2). Given the severity of this disease, it is important to consider the risk factors of kidney cancer so that we may lower our risk through lifestyle-based intervention and identify those at high risk due to genetic predisposition.
Around 90% of all kidney cancers in adults are renal cell carcinomas (RCC) (3). The most commonly occurring type of RCC is clear cell carcinoma, which comprises around 70% of all RCCs (3). A further 15% of RCC is papillary renal cell carcinoma, which is a cancer that originates from a different kind of kidney cell than clear-cell carcinoma (3). Previously, scientists thought of kidney cancer as one singular disease. Still, now it has become clear that kidney cancer is an amalgamation of diseases that can originate from different cell types via a multitude of mechanisms (4). Recognizing this difference has helped scientists better address this collection of diseases that all happen to impact the kidney (4).
Genetic Risk Factors
Two types of genetic inheritance patterns impact the rate of kidney cancer: inherited gene mutations, and inherited cancer syndromes.
Inherited gene mutations involve changes to vital genes which are passed from parent to child. For example in clear cell carcinoma, the Von Hippel-Lindau (VHL) gene is the most commonly altered gene culprit, responsible for kickstarting the change from normal to cancer cell (5). The VHL gene is an important member of the cell’s growth regulation machinery. Errors in the VHL gene derail normal cellular growth and replication cycles, leading to changes that promote kidney cancer (5).
Inherited cancer syndromes, also known as family cancer syndromes, are similar to inherited gene mutations in that they involve the inheritance of genetic mutations from parent to child. However, inherited cancer syndromes are a group of genetic disorders that tend to further increase the likelihood of cancer relative to inherited gene mutations alone (5). Some examples of hereditary cancer syndromes that have been linked to kidney cancer include Von Hippel syndrome, tuberous sclerosis complex, and Birt-Hogg-Dubé syndrome (6). While these inherited cancer syndromes have massive cancer-causing potential, their rate of occurrence is low (6). Ultimately these inherited cancer syndromes only comprise 5%-8% of all cases of kidney cancers (5). When patients with family cancer syndromes do develop kidney cancer, they tend to have tumours in both kidneys (bilateral kidney cancer) (5). They may also have several tumours within each kidney (multifocality), and develop kidney cancer at a younger age compared to kidney cancer patients without inherited genetic disorders (5).
Aside from these heritable risk factors, other causes of kidney cancer involve genetic mutations caused by some stimulus. This stimulus is usually exposure to chemicals from the environment or comorbidities (other illnesses) like diabetes that damage the kidney over a long period of time.
Environmental Risk Factors
Smoking, obesity, and high blood pressure are preventative risk factors for kidney cancer.
Smoking
In 2022, smoking was classified as a moderate risk factor for kidney cancer by the International Agency for Research on Cancer (IARC) (7). Cigarette smoke contains polycyclic aromatic hydrocarbons and beta-naphthylamine; cancer-causing molecules that are filtered through the nephron, the functional unit of the kidneys (7). These molecules are known as carcinogens. Carcinogenic molecules from smoke are known to enter the body’s circulation as reactive metabolites that result in DNA damage and inflammation, and ultimately increase cancer risk (8).
The relationship between smoking and kidney cancer development has been classified through a dose-dependent relationship, where individuals who have never smoked are at a lower risk for developing kidney cancer (7). The risk of kidney cancer increases with an increasing number of cigarettes smoked per day (7). In addition, smoking cessation for more than 10 years showed a significantly lower risk for kidney cancer, however, it was still as low as the risk for individuals who have never smoked (7,8). There is a 26% higher cancer risk for individuals who have smoked at any time of their life compared to never-smokers (7). The specific mechanisms through which tobacco smoke affects the kidneys are still unknown (7). Despite that, the evidence from studies determining the effects of smoking on kidney cancer development strongly suggests that there is a direct relationship between the number of cigarettes smoked and increasing cancer risk (9).
Hypertension
Hypertension, or high blood pressure, can damage blood vessel walls and the kidney’s filtering system, increasing the risk of kidney cancer (8). Factors like oxidative stress, characterized by low antioxidant levels and the formation of reactive oxygen species, highly reactive and unstable chemicals that damage cells, and lipid changes are worsened by hypertension and contribute to the risk of kidney cancer (7,10).
There is a consistent correlation between hypertension and kidney cancer risk (9). In the United States, hypertensive individuals have double the risk for kidney cancer than individuals with normal blood pressure (120 mmHg/80 mmHg) (8). Poorly managed hypertension following diagnosis further increases this risk, however, if the hypertension is properly controlled, the chance of developing kidney cancer can be lowered (8). Additionally, patients with diabetes are twice as likely to struggle with high blood pressure as patients without diabetes (11). Therefore, diabetics who manage their blood pressure by reducing salt intake, decreasing stress exercising regularly to maintain a healthy weight, and avoiding excessive alcohol intake and smoking can also help control hypertension, significantly decreasing the overall risk for kidney cancer (11).
Obesity
The IARC highlights obesity as a major risk factor for many cancers, including kidney cancer (7). About 20% of kidney cancers are associated with the systemic effects of obesity (7). Chronic inflammation is one of the many pathways linked to obesity that is known to cause kidney cancer (7). Obesity keeps the body in a chronic inflammatory state by continuously releasing pro-inflammatory factors through adipose tissue (12). Chronic inflammation is long-term, persistent inflammation with continuous production of growth factors and the growth and division of cells and blood vessels, another notable characteristic of cancer development (13).
Interestingly, while obesity increases kidney cancer risk, it paradoxically has a positive impact on kidney cancer prognosis (7). This phenomenon is known as the “obesity paradox” but the specific mechanism through which this occurs is poorly understood (8,9). Despite its protective effect on kidney cancer, obesity is still a significant risk factor for numerous health conditions including other cancers (9). All in all, cancer risk can be reduced by maintaining a healthy weight through the management of diet, exercise, and stress.
Preventative Measures
The many preventative measures that are designed to address kidney cancer highlight proper diet and exercise for weight management, and avoiding bad habits such as smoking. Since high blood pressure is a risk factor for kidney cancer, proper management of blood pressure with medication is vital for late-life kidney health (14). Research shows that around 1 in every 2 patients fail to take blood pressure medication regularly despite being instructed by healthcare workers (14). Adhering to a schedule for taking medication prevents forgetfulness. Long-term, careful management of blood pressure prevents a lot of circulatory issues as well as kidney disease and cancer (14).
Overall, kidney cancer is influenced by genetic and lifestyle risk factors and is further exacerbated by comorbidities. Understanding the risk factors associated with kidney cancer development allows for the implementation of preventative measures in the form of lifestyle changes. In addition, early detection through regular screening can allow physicians to identify symptoms associated with kidney cancer, allowing for improved outcomes.
References
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11. Diabetes and High Blood Pressure. https://www.hopkinsmedicine.org/health/conditions-and-diseases/diabetes/diabetes-and-high-blood-pressure.
12. Ellulu MS, Patimah I, Khaza’ai H, Rahmat A, Abed Y. Obesity and inflammation: the linking mechanism and the complications. Archives of Medical Science : AMS. 2017;13(4): 851–863. https://doi.org/10.5114/aoms.2016.58928.
13. Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and Cancer. Annals of African Medicine. 2019;18(3): 121–126. https://doi.org/10.4103/aam.aam_56_18.
14. Hypertension: What You Need to Know as You Age | Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/high-blood-pressure-hypertension/hypertension-what-you-need-to-know-as-you-age.