What causes bladder cancer?

Until my diagnosis, I was unaware of bladder cancer, its risk factors or its cause. Although it is fairly common, it is not one of the well known cancers like breast cancer that attracts media attention. This may be because the leading risk factor for bladder cancer is smoking and the social stigma. 

In this post, I will look at the risk factors for bladder cancer and the causes, including the urinary microbiome’s role in DNA mutations.

What are the risk factors for bladder cancer?

There are many risk factors that make a person more likely to develop bladder cancer. Some you can control, like smoking, and others you cannot.

• Smoking – Smoking is the most common risk factor for bladder cancer
• Workplace exposures – Certain industrial chemicals have been linked with bladder cancer
• Certain medicines or supplements 
• Arsenic in drinking water
• Not drinking enough fluids
• Race and ethnicity – Whites are more likely to develop bladder cancer than other races. 
• Age – 9 out of 10 people with bladder cancer are older than 55
• Chronic bladder irritation and infections, including long-term use of catheters
• Genetics and family history

I ticked the smoking, race, and age risk factor boxes. Although I’d given up smoking for ten years, I’d smoked in my twenties in my forties. It looked like I’d scored an own goal.

However, it’s all very well to be aware of the risk factors for bladder cancer. But what is it about those risk factors that actually cause bladder cancer? Until recently, researchers didn’t exactly know what causes most bladder cancers. But pioneering research into the urinary microbiome reveals the inflammatory mechanism linking chemicals such as those found in smoking to changes in the DNA and the development of BC. The vitality of the urinary microbiome is, therefore, emerging as a critical factor influencing bladder cancer development and therapeutic responsiveness.

The role of the urinary microbiome in bladder cancer

Research into the urinary microbiome is relatively new. The Human Microbiome Project in 2007 didn’t even consider the urinary microbiome. Advances in detecting microbes have discredited the once widely-held notion that the bladder is a sterile environment. Indeed, the healthy bladder is home to a wide assortment of bacterial species. 

A recent study published in the IOS Press Open Library examined the role of the urinary microbiome in bladder cancer. Several research groups have identified the role of a protective urinary microbiome in healthy individuals. Other studies have also found alterations in the urinary microbiome of patients with bladder cancer compared with healthy individuals. Additionally, the urinary microbiome differs between men and women. These differences are associated with a lower incidence of bladder cancers in women. 

Evidence suggests that chronic inflammation may be critical in various diseases, including bladder cancer. This hypothesis stems from inflammatory cells observed in the bladder. Chronic inflammation may drive the progression of bladder cancer by activating a series of inflammatory molecules and signals. The urinary microbiome plays a role in establishing the inflammatory environment that may facilitate the development and progression of bladder cancer. Chronic inflammation caused by dysbiosis in the urinary microbiome may promote the development of bladder cancer.

The figure above shows the complex relationship between the urinary microbiome and the host. It is affected by many factors, including antibiotic use, anatomical structures, surgical manipulation, diet, genetics, and age. 

The microbiome impacts bladder cancer at each stage of its development and, therefore, immune responses. Studies show that the vitality of the urinary microbiome may have a significant role in immunotherapy responses. One study concluded that probiotics injected into the bladder could be a potential strategy to support immunotherapy. 

The role of DNA mutations in bladder cancer

It seems that specific changes in our genetic DNA inside normal bladder cells can make them grow abnormally and form cancers. Our parents are the source of our genes, but DNA affects more than just how we look. Mutations that turn on genes that help cells grow and divide or turn off anti-tumour genes can cause cancers. 

Most DNA mutations related to bladder cancer happen through environmental factors rather than genetic inheritance. Some of these mutations result from cancer-causing chemicals or radiation exposure. For example, chemicals in tobacco are absorbed into the blood, filtered by the kidneys, and disrupt the urinary microbiome’s vitality. This disruption leads to inflammation followed by changes in bladder cell DNA and, consequently, cancer development. 

Chemicals in the workplace may also disrupt the urinary microbiome in the same way. 

Some people inherit genes from their parents that increase the risk of bladder cancer. However, bladder cancer does not often run in families except where there are shared environmental risks like smoking. Inherited gene mutations are, therefore, not a significant cause of BC. 

Can Bladder Cancer Be Prevented?

There is no sure way to prevent bladder cancer. Some risk factors, like age, gender, race, and family history, can’t be controlled. But there might be things you can do that could help lower your risk.

• Don’t smoke – this is obvious but may be hard to implement due to cognitive dissonance.
• Limit exposure to chemicals in the workplace
• Drink plenty of liquids
• Eat mainly fruits and vegetables, don’t overeat, and eat real food – a Mediterranean Diet is an excellent place to start.

What can I do to maintain a healthy urinary microbiome?

Unlike the gut microbiome, there is little information known about how to promote a healthy urinary microbiome. Besides avoiding tobacco smoke and workplace chemicals, eating a healthy diet is likely to benefit the urinary microbiome as a preventative and therapeutic measure in supporting immunotherapy for BC. 

I also suspect that taking cranberry as a supplement helps maintain a healthy urinary microbiome by suppressing bacterial pathogens known to cause UTIs. But so far, all the studies on cranberry extracts and UTIS have only focussed on the gut microbiome. A study published in the National Library of Medicine found that cranberry extracts enrich beneficial bacteria in the gut microbiome while reducing pathogenic bacteria that cause UTIs. 7

Conclusion

The risk factors for bladder cancer are well known. The causes of bladder cancer are just beginning to emerge with the role of the urinary microbiome at its core. While there are risk factors that you cannot control, there are some, such as smoking, that you can. Even after receiving a diagnosis for BC, you may support your response to treatment and healing by maintaining a healthy urinary microbiome through diet and the right supplements.

References

1. What Causes Bladder Cancer?; Available at URL: https://www.cancer.org/cancer/bladder-cancer/causes-risks-prevention/what-causes.html
2. The Urinary Microbiome and Bladder Cancer: Susceptibility and Immune Responsiveness; Available at URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605348/#:~:text=Recently%20a%20commensal%20urinary%20microbiome,cancer%20development%20and%20therapeutic%20responsiveness
3. Profiling the Bladder Microbiota in Patients With Bladder Cancer; Available at URL: https://www.frontiersin.org/articles/10.3389/fmicb.2021.718776/full
4. Profiling the Bladder Microbiota in Patients With Bladder Cancer; Available at URL: https://www.frontiersin.org/articles/10.3389/fmicb.2021.718776/full
5. The inflammatory microenvironment and the urinary microbiome in the initiation and progression of bladder cancer; Available at URL: https://www.sciencedirect.com/science/article/pii/S2352304220301276
6. Characterization of the urinary microbiota in bladder cancer patients; Available at URL: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.6_suppl.535
7. Cranberry extracts promote growth of Bacteroidaceae and decrease abundance of Enterobacteriaceae in a human gut simulator model; Available at URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850528/#:~:text=Cranberry%20extracts%20and%20whole%20cranberry%20powder%20modulate%20a%20human%20gut,reservoir%20of%20UTI%2Dcausing%20Enterobacteriaceae