Introduction

Renal cancer, otherwise known as kidney cancer, is a major cancer that develops in the parenchymal cells (functional cells) of the kidneys. It can occur in the form of renal cell carcinomas (RCCs), transitional cell carcinomas (TCCs), and Wilms’ tumours. The incidence of RCCs has shown a steady increase since the 1960s and now makes up approximately 80-85% of kidney cancer cases, most of which occur in Europe and North America.^1,2 TCCs are relatively less common and make up around 8% of the total reported cases of kidney cancer.¹ 

Renal cancer can be influenced by a multitude of factors, the most common being smoking, alcohol consumption, obesity, diabetes, and hypertension. Its onset is typically seen after the age of 45, often peaking at 75 years. Approximately 400,000 cases are reported every year, and men are also twice as likely to be diagnosed.² Some frequently reported symptoms include blood in the urine, fever, and fatigue. 

Types of kidney cancer

Kidney cancer can be broadly classified as RCC, TCCs, and Wilms’ tumours, which are outlined below. 

Renal cell carcinomas

RCCs are the most common form of kidney cancer and originate in the tubules of the kidney. In their initial stages, RCCs can be undetectable; therefore, medical attention must be immediately sought once symptoms appear. Depending on the nature of the tumour, RCCs can be further classified as:

• Clear cell carcinomas are characterised by pale and clear cancer cells. Patients can exhibit the conventional symptoms of kidney cancer, but can also be asymptomatic
• Papillary carcinomas are compact and heterogeneous. They often occur sporadically and can affect prognosis depending on their type
• Collecting duct carcinomas develop in the distal convoluted tubules of the kidney and have a tubular-like architecture. They are also typically rare, aggressive, and tend to metastasise rapidly
• Chromophobe carcinomas are the third-most common form of RCC, with relatively larger and pale/brown cancer cells

Transitional cell carcinomas

TCCs initially develop in the tissue lining of the kidneys, particularly in the urinary tract, consequently leading to bladder cancer. TCCs can be papillary or non-papillary and can produce symptoms that vary depending on the site of the tumour and its severity.

Wilms’ tumour

Wilms’ tumours are a rare form of renal cancer that mostly occurs in children. These cancers can be easily treated and are associated with a great survival rate. Symptoms typically include nausea, vomiting, and the presence of a tender abdominal mass. 

Epidemiology of kidney cancer

Kidney cancer ranks 14th on the list of most common cancers worldwide, but has the highest incidence, particularly in Western countries. It globally accounted for approximately 139,000 deaths in 2017 and 156,000 deaths in 2022, highlighting an increase in its incidence in the general population.³ 

Despite its rampant occurrence, the exact cause of kidney cancer remains unclear. Previous studies have also highlighted an increase in the presence of kidney cancer in developed countries than in developing countries.³ 

Many factors like smoking, genetics, a high body mass index, and metabolic disease have been established as contributing factors, thus making renal cancer a rather multifactorial health issue.

General overview of some common risk factors of kidney cancer 

Alcohol consumption

The consumption of alcohol has been widely documented to have negative effects on biochemical responses and increase an individual’s risk for many diseases, especially cancer. However, with respect to kidney cancer, this statement has been up for debate. Several meta-analyses have reported an inverse relationship between alcohol consumption and the risk of developing kidney cancer.^2,4 An increase of 12g in ethanol consumption was associated with a 5% decrease in the likelihood of kidney cancer.⁴ Moreover, it is hypothesised that the increase in insulin sensitivity that occurs as a result of an increase in alcohol intake is responsible for the protective effects of alcohol on kidney cancer.²

Obesity

Obesity or excessive body weight is the second key contributor to the incidence of kidney cancer. Studies have reported a direct relationship between high body weight in the earlier stages of life to the likelihood of developing kidney cancer as an adult.² An increase in waist size and waist-to-hip ratio also significantly amplified the risk of developing renal cancer.² Mechanisms that contribute to this may involve specific gene expression and inflammatory pathways.

Other factors

Genetics and a family history of kidney cancer or Chronic Kidney Disease (CKD) can play important roles in predicting the development of cancer in an individual. Other participating factors may also include height and occupational exposure to trichloroethylene, arsenic, and lead.^2,3 Furthermore, genetic factors like the presence of Von-Hippel Lindau syndrome and Birt-Hogg-Dube syndrome increase an individual’s susceptibility to kidney cancer.² 

Smoking as a risk factor 

Cigarette smoking has long since been a global health issue and has been named the major contributor to the onset of many cancers, including but not limited to lung cancer, mouth cancer, and kidney cancer. The inhalation of carcinogens drive DNA damage and facilitates the formation of tumours through different pathways. It is a major health hazard that heightens the risk of presenting with fatal health concerns, thereby exerting significant negative effects on mortality. Cancer is one such fatality, with smoking accounting for 17% of kidney cancer occurrences globally.⁵

Cigarettes are typically composed of nicotine, heavy metals like cadmium, and various other carcinogenic substances, most of which are known to impair kidney function by progressively damaging microvessels, impacting filtration rates, and increasing blood pressure.⁶ The copious amounts of nicotine and cadmium in cigarettes primarily contribute to glomerular atrophy and fibrosis, which accelerate the progression of kidney disease.^6,7 Kidney cancer and CKD may go hand-in-hand, often displaying a cause-and-effect relationship - the presence of CKD usually increases a person’s susceptibility to kidney cancer.^7,8 Over time, these effects can accumulate and create structural abnormalities in the kidney, further causing kidney disease.^6,7 Chronic smoking can damage the proximal and distal tubules of the kidney and promote cell death and fibrosis.⁷ The consumption of tobacco also results in immune suppression, causing a decline in immune cell counts, thereby facilitating tumour growth.¹ This is further compounded in individuals with histories of hypertension and diabetes, where renal abnormalities are almost always observed. 

Many studies have, therefore, been conducted by studying the dose-response relationship between smoking and kidney cancer. This allows for a comprehensive analysis of the impact of cigarette smoking on cancer prognosis and overall health. A meta analysis reported a heightened risk of 39% in current smokers and 20% in former smokers.⁹ The consumption of even five cigarettes a day was associated with an 18% higher risk of developing kidney cancer.⁹ In another study, a decrease in the rate of cancer progression (~56%) and mortality (~50%) in patients with RCCs was observed as a result of quitting smoking.⁵ This study also reported a 60% increase in the risk of death and disease progression in patients who were active smokers during diagnosis.⁵

To prevent is to cure

Tobacco smoking remains the major contributor to cancer incidence worldwide, being responsible for nearly 15% of all cancer cases in the United Kingdom.¹⁰ The rise in the prevalence of modifiable risk factors makes early diagnosis of the utmost importance. The early diagnosis of RCC lesions boasts a survival rate of nearly 93% and is primarily due to advanced diagnostic methods like Magnetic Resonance Imaging (MRI) and Computed Tomography (CT).⁹ However, individuals with late-stage RCCs report poor mortality rates.

Advancements in healthcare have paved the way for diverse pharmacological alternatives such as tyrosine kinase inhibitors and immune checkpoint inhibitors. Urine biomarkers like PLIN2 and AQP1 have been used as screening checkpoints for the early detection of some RCC subtypes.¹¹ Incorporating the use of novel transcriptomics and metabolomics analyses as part of the screening process would also be beneficial as these techniques provide important insights into the metabolic, genetic, and biochemical pathways that may be involved in the pathology of such cancers.^2,11 In addition, nephron-sparing surgery and image-guided ablation can be used to ensure sustained cancer-free survival.¹²

While progress in science and technology has made treatment possible, there is still a long road ahead. More research is needed to thoroughly understand cancer pathology and identify specific biomarkers. While genetic predisposition cannot be controlled, making positive changes to one’s lifestyle can significantly influence the probability of developing cancer. Regular exercise combined with healthy eating habits, eliminating tobacco use, and limiting alcohol consumption is an excellent approach to maintaining optimal health and preventing the onset of a debilitating disease. 

Summary

• Despite being one of the most commonly occurring cancers worldwide, the aetiology of renal cancer has not been fully understood. It can occur in different forms and can be present in both children and adults
• The major risk factors for kidney cancer include, but are not limited to, smoking, obesity, genetics, and occupational exposure to carcinogens like arsenic and lead
• Around 20% of people diagnosed with kidney cancer are active smokers⁵, and smoking has been scientifically proven to increase the incidence of kidney cancer, as well as CKD. While this can be lowered by quitting smoking, it is important to note that the decrease in risk cannot be compared to that in people who never smoke
• Prevention is ultimately the best cure, but advancements in diagnostic tools have made the road to treatment much easier. New avenues of treatment that enable the early detection of cancerous masses are also being studied