Smoking and Bladder Cancer

You may know that cigarette smoking is the leading cause of preventable disease and death in the US, but did you know that smoking is also the number one preventable risk factor for bladder cancer? The good news is that fewer people are now smoking, and reducing exposure to tobacco smoke – as an active smoker or through secondhand sources – decreases bladder cancer risk and improves outcomes for those diagnosed with the disease.

• Can smoking cause bladder cancer?
• Smoking and bladder cancer: what is the risk?
• Can second-hand smoke cause cancer?
• How does smoking affect the bladder?
• Vaping versus smoking: does vaping cause cancer?
• Is vaping safer than smoking?
• Quitting smoking reduces cancer risk
• Looking to quit? Here’s where to get help
• Cxbladder testing can detect or rule out bladder cancer

Can smoking cause bladder cancer?

Smoking causes cancer in at least 15 areas of the body, including the bladder.¹ In the US, smoking causes around half of all bladder cancers in both men and women,² making it the leading preventable risk factor, well ahead of workplace exposure to industrial chemicals.

Smoking and bladder cancer: what is the risk?

The more you smoke, the higher the risk. Bladder cancer risk increases with smoking duration (the number of years you have smoked) and intensity (the number of cigarettes smoked each day), although duration appears to have a greater effect.³ Overall, smokers are at least three times more likely than non-smokers to develop bladder cancer. An analysis of data from multiple previously published studies (this is known as a meta-analysis) found that, relative to people who had never smoked, the risk of getting bladder cancer was 3.5 times higher for current smokers, improving to 2 times higher for former smokers (see bar graph).⁴ A second meta-analysis found a similar increase in bladder cancer risk for male and female smokers, but a higher risk in European compared with Asian populations.⁵ Some genetic variants are also linked to a higher increase in bladder cancer risk for smokers.⁶

Can second-hand smoke cause cancer?

Second-hand smoke (SHS), or involuntary smoking, exposes children, pets and non-smokers to the same carcinogens inhaled by smokers. There is no safe level, but home and workplace exposure are a particular concern, with a 20–30% increase in lung cancer risk for non-smokers exposed to SHS in these settings.⁷ While more research is needed to confirm potential links to other cancers, and results for bladder cancer have been inconsistent, a meta-analysis of 14 studies found that second-hand smoke exposure was linked to a 22% increase in bladder cancer risk.⁸ This is lower than the risk increase shown in the figure. It is reasonable to conclude that SHS significantly increases the risk of developing bladder cancer, although there is uncertainty over the precise level of risk.

Exposure to SHS can be measured by blood levels of cotinine, a chemical formed in the body after nicotine exposure. Linked to this, encouraging findings from the National Health and Nutrition Examination Survey (NHANES) show the percent of non-smokers exposed to SHS decreased from 88% in 1988 to 25% in 2014, but around two of every five children were still exposed to the harmful effects of SHS.⁹ Pets are also vulnerable! Dogs, cats and birds that live with smokers have an increased risk of cancer.¹⁰

In those who are diagnosed with bladder cancer, smoking leads to worse outcomes. Notably, being a smoker at the time of major bladder cancer surgery (cystectomy) increases the risk of serious complications, infections, and death after surgery.¹¹ Smokers are also half as likely to respond to preoperative chemotherapy, more likely to have their bladder cancer return after surgery, and more likely to die of cancer.¹²

How does smoking affect the bladder?

Cigarette smoke contains over 7,000 chemicals, including around 70 known to be cancer-causing agents (carcinogens).¹³ Some of the most damaging carcinogens in cigarette smoke include polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines, 1,3-butadiene, benzene, aldehydes, and ethylene oxide.¹⁴ Two of the aromatic amines in cigarette smoke (2-naphthylamine and 4-aminobiphenyl) are a major cause of bladder cancer in smokers.¹⁴

How does smoking cause cancer of the bladder?

In its normal functioning, the body removes a variety of toxins through the urine. When you inhale, harmful chemicals in cigarette smoke are absorbed from the lungs into the blood before being filtered through the kidneys and collecting in the bladder. During the hours that urine sits in your bladder, the bladder lining is directly exposed to carcinogens. Some of these chemicals bind to and damage DNA, eventually leading to mutations and tumor formation, while others increase cancer risk indirectly, for example by harming the immune system and promoting inflammation.

Aside from causing cancer, smoking also irritates the bladder. Smoking can worsen symptoms of overactive bladder and interstitial cystitis (a chronic, painful bladder condition that is more common in women), such as urgent and frequent need to urinate. Coughing spasms can also provoke urine leakage in smokers. Other urologic conditions associated with smoking include kidney cancer, kidney stones, erectile dysfunction, and infertility.

Vaping versus smoking: does vaping cause cancer?

Though vaping exposes the user to fewer toxic substances than smoking, it is not harmless: the aerosol inhaled and exhaled during vaping may contain nicotine, heavy metals, and carcinogens.¹⁵ Encouragingly the levels of carcinogens and toxins in e-cigarettes are much lower than in cigarettes, and short-term studies suggest that smokers who switch to vaping do experience reduced exposure to carcinogens.¹⁶ However, it is too soon to know the long-term risks, including whether vaping can cause cancer. Currently there are grounds for concern: 63 toxic or carcinogenic metabolite biomarkers have been identified in the urine of vapers, including several with a strong known link to bladder cancer.¹⁷

Is vaping safer than smoking?

Clearly the healthy option is not to smoke or vape but, for adults who currently smoke cigarettes, switching to vaping is probably safer than smoking and may help with quitting completely. Combining vaping and cigarette smoking results in more potentially harmful chemicals being detected in the urine – it’s better to switch completely.¹⁸

Quitting smoking reduces cancer risk

Stopping smoking reduces the risk of many cancers over time. For bladder cancer, the risk drops steadily as the number of years since quitting smoking increases, with a definite reduction within 10 years.¹⁹ If this seems slow, remember that most cancers take many years to develop. Of course, quitting smoking has numerous additional health benefits, many of which occur rapidly, including a decrease in heart rate and blood pressure within 20 minutes and a reduction in carbon monoxide levels in the blood within hours, which increases the blood's ability to carry oxygen.^20,21 Improved circulation and lung function (such as reduced phlegm, coughing and wheezing) can occur within a few weeks.

Due to the level of harm caused by smoking, quitting ultimately increases life expectancy by up to 10 years, depending on the age when you quit.²⁰ Although the benefit is greater the earlier you stop, it’s never too late – quitting has many health benefits regardless of smoking duration, including if you’ve already been diagnosed with a smoking-related disease. In fact, a bladder cancer diagnosis can provide strong motivation, enabling smokers to successfully quit after decades of smoking.²²

Looking to quit? Here’s where to get help

Though a range of factors may have influenced your decision to start and continue smoking, quitting is a personal decision – you must want to stop. Many people find it takes several attempts but do ultimately succeed, as can be seen in the declining rates of smoking in the US.²³ Notably, quit rates do improve with support from others and specialized medication, so it’s worth trying different approaches to find what works for you. FDA-approved medications for stopping smoking include nicotine-replacement therapy (e.g., patches, gum and lozenges) and two prescription medications, varenicline and bupropion.

It's important to note that e-cigarettes (vaping) are not approved by the FDA for smoking cessation. Evidence from randomized trials does suggest that vaping with nicotine-containing e-cigarettes increases quit rates compared with nicotine replacement therapy.²⁴ However, it’s not yet known whether people will continue vaping, or successfully quit nicotine altogether.

A range of useful and free online resources are available to help you clarify your own motivation to quit, make a plan, get tips to manage cravings, and recover from slip-ups. Recommended sites include Smokefree.gov and the Centers for Disease Control and Prevention (CDC) Tips From Former Smokers guide to How to quit smoking.

Activities to consider include:

• Build a quit plan
• Learn more about nicotine replacement therapy and smoking cessation and medications: fact vs fiction
• Get daily texts from SmokefreeTXT by texting QUIT to 47848. (This is a 6–8 week program for adults; additional text programs are available.)
• Try an app like QuitGuide and QuitSTART to identify your smoking patterns and triggers, then develop a customized quit plan
• Get quick answers about quitting smoking from the National Cancer Institute using live chat

Free and confidential phone helplines:

To get individualized advice and referrals from a trained counselor over the phone:

• Quitline:13 7848

Resources for people living or working with smokers

Being exposed to the dangerous effects of second-hand smoke when it’s not your choice is a challenge. When it comes to family and friends, the American Cancer Society has tips on how to help someone quit smoking, but these do assume that the person is trying to quit. When this is not the case, two UK-based sites have advice:

• Action on Smoking and Health (ASH), Wales: What to do if you live with a smoker –conversations about quitting, practical tips (e.g., suggesting the person use nicotine replacements to manage cravings in the house).
• The Mix: How can I cope with living with smokers? While aimed at young people, many points are relevant to anyone living with a smoker who may have no intention of quitting.

Beyond the immediate household, SHS exposure is a particular problem in apartment complexes and assisted-living facilities, where smoke can permeate the building through hallways and even ventilation systems. The American Nonsmokers' Rights Foundation (ANRF) has information and resources that may be useful: Are You Exposed to Secondhand Smoke In Your Home?

Workplace exposure to SHS is now less common due to legislation in many states, as well as smoke-free workplace policies set by employers. If you are exposed to SHS at work, the non-profit Workplace Fairness has a Q&A on Smoking and the Workplace and the ANRF also covers this issue: Smokefree Workplaces Are Good For Health & Business.

If you are at risk, Cxbladder testing can rule out bladder cancer

If you’re a current or former smoker concerned about your risk of developing bladder cancer, early detection gives the best chance for successful treatment. Blood in the urine (hematuria) - either visible as red or pink coloring or not visible to the naked eye - is the number one symptom to be aware of. If you experience blood or are concerned about risk, make an appointment to speak with your doctor.

If tests confirm the presence of blood, ask your doctor about Cxbladder. Cxbladder is a non-invasive genomic urine test optimized for the rule out of urothelial bladder cancer, the most common form of the disease. The test analyzes five biomarker genes to quickly and accurately rule out the disease, reducing the need for further invasive tests.
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