A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.The following factors may raise a person’s risk of developing bladder cancer:
Age
The risk of bladder cancer increases with age. About 9 out of 10 people with bladder cancer are older than 55.
Arsenic
Arsenic in drinking water has been linked with an increased risk of bladder cancer in some parts of the world. The chance of being exposed to arsenic depends on where you live and whether you get your water from a well or from a public water system that meets the standards for arsenic content. For most Americans, drinking water is not a major source of arsenic.
Bladder birth defects
Before birth, there is a connection between the belly button and the bladder. This connection, called the urachus, normally goes away before birth. If part of this connection remains after birth, it could become cancerous. Cancers that start in the urachus are usually adenocarcinomas, which are made up of malignant gland cells. About one-third of the adenocarcinomas of the bladder start here. However, this is still rare, accounting for less than a half of 1% of all bladder cancers.
Another rare birth defect called exstrophy greatly increases a person’s risk of developing bladder cancer. In bladder exstrophy, both the bladder and the abdominal wall in front of the bladder fail to close completely during development and are fused together. This leaves the inner lining of the bladder exposed outside the body. Surgery soon after birth can close the bladder and abdominal wall (and repair other related defects), but people who have this still have a higher risk for urinary infections and bladder cancer.
Diet
• Certain medicines or herbal supplements
According to the US Food and Drug Administration (FDA), use of the diabetes medicine pioglitazone (Actos) for more than one year may be linked with an increased risk of bladder cancer.
Dietary supplements containing aristolochic acid (mainly in herbs from the Aristolochia family) have been linked with an increased risk of urothelial cancers, including bladder cancer.
• Low fluid consumption
Not drinking enough fluids may increase the risk of bladder cancer. People who drink a lot of fluids each day have a lower rate of bladder cancer. This is thought to be because they empty their bladders often. By doing this, they keep chemicals from lingering in their bodies.
Family history and genetic conditions
People who have family members with bladder cancer have an increased risk of getting it themselves. In some cases, these family members may all be exposed to the same cancer- causing chemical. They may also share changes in some genes (like GST and NAT) that cause their bodies to be slow to break down certain toxins, which can make them more likely to develop bladder cancer.
A small number of people inherit a gene syndrome that increases their risk for bladder cancer. For example:
- A mutation of the retinoblastoma (RB1) gene can cause cancer of the eye in infants, and also increases the risk of bladder cancer.
- Cowden disease, caused by mutations in a gene called PTEN, is linked mainly to cancers of the breast and thyroid. People with this disease also have a higher risk of bladder cancer.
- Lynch syndrome (also known as hereditary non-polyposis colorectal cancer, or HNPCC) is linked mainly to colon and endometrial cancer. People with this syndrome also have an increased risk of bladder cancer, as well as cancer of the ureters.
Gender
Bladder cancer is much more common in men than in women.
Immune system
• Organ transplant
Bladder cancer risk is around threefold higher among renal transplant recipients, compared with the general public, a meta-analysis showed.
Infections
• Chronic bladder irritation and infections
Urinary infections, kidney and bladder stones, bladder catheters left in place a long time, and other causes of chronic bladder irritation have been linked with bladder cancer (especially squamous cell carcinoma of the bladder), but it is not clear if they actually cause bladder cancer.
• Human papillomavirus (HPV)
One study showed a doubling in risk of bladder cancer in patients with condylomata acuminata (genital warts). Genital warts are caused by infection with the human papillomavirus (HPV), and a meta-analysis showed a three-fold increased risk associated with HPV infection.
• Schistosomiasis
Schistosomiasis (also known as bilharziasis), an infection with a parasitic worm called Schistosoma hematobium that can get into the bladder, is also a risk factor for bladder cancer. In countries where this parasite is common (mainly in Africa and the Middle East), squamous cell cancers of the bladder are seen much more often. This is an extremely rare cause of bladder cancer in the United States.
Ionising radiation
A very small proportion of bladder cancer cases are associated with therapeutic irradiation in the pelvic region, for example for testicular cancer or cervical cancer. Men with a history of prostate cancer, both those treated with and without radiotherapy, have an increased risk of bladder cancer. The risk of bladder cancer has been shown to be increased two-fold in women treated for cervical cancer without radiotherapy, which may be due to shared risk factors such as smoking. A risk increase was also seen in women treated with radiotherapy- the risk was almost six-fold for women treated for cervical cancer 40 or more years previously.
A study published in December 2011 has estimated that 2.6% of bladder cancer cases in men and 2.3% in women in the UK in 2010 were linked to radiation exposure, with most of these cases linked to exposure to diagnostic radiation.
Medical conditions and treatments
• Chemotherapy and radiation therapy
Long-term use of the chemotherapy drug cyclophosphamide (Cytoxan) can irritate the bladder and increase the risk of bladder cancer. People taking this drug are often told to drink plenty of fluids to help protect the bladder from irritation and decrease the risk of bladder cancer.
People who are treated with radiation to the pelvis are more likely to develop bladder cancer.
• Disability
Paraplegics have a greatly increased risk of squamous cell carcinomas of the bladder, due to their disposition to chronic urinary tract infection. Kidney and urinary stones may also slightly increase risk.
• Gastric ulcers
There is limited evidence that a history of gastric ulcer increases risk.
Occupational exposures
It has been estimated that, in the UK, around 7% of bladder cancer cases in men and 2% in women are linked to occupational exposures. This proportion may be higher in countries with less-regulated industrial processes.
• Aromatic amines
In 1895 Rehn reported cases of bladder cancer in a German aniline dye factory. This led to occupational studies in other countries but it was not until the 1950s that the risk from aromatic amines, particularly benzidine and a-and ß-naphthylamine, was established by Case.
Aromatic amines were widely used in the manufacture of dyes and pigments for textiles, paints, plastics, paper and hair dyes, in drugs, pesticides and as antioxidants in the rubber industry. Production of ß-naphthylamine ceased in the UK in 1952 (its use was withdrawn from the rubber and cable industry prior to this in 1949) and in 1953 bladder cancer became, and still is, a prescribed industrial disease.
• Diesel engine exhaust
In June 2012, IARC classified diesel exhaust as associated with an increased risk of bladder cancer. This was based on limited evidence mainly from studies of highly-exposed workers.
• Polycyclic aromatic hydrocarbons (PAH)
Exposure to polycyclic aromatic hydrocarbons (PAH), which are by-products of combustion processes and therefore present in a range of industries, has also been investigated. It is calculated that about 4% of bladder cancer cases in European men are due to exposure to PAH. A recent meta-analysis showed a risk increase of about 30% for bladder cancer in painters and the International Agency for Research on Cancer classifies occupation as a painter as a cause of bladder cancer.
Personal history of bladder or other urothelial cancer
Urothelial carcinomas can form in many areas in the bladder as well as in the lining of the kidney, the ureters, and urethra. Having a cancer in the lining of any part of the urinary tract puts you at higher risk of having another tumor. The tumor can form in the same area as before, or in another part of the urothelium (lining). This is true even when the first tumor is removed completely. For this reason, people who have had bladder cancer need close, routine medical follow-up.
Race and ethnicity
Whites are about twice as likely to develop bladder cancer as African Americans. Hispanics, Asian Americans, and American Indians have slightly lower rates of bladder cancer. The reasons for these differences are not well understood.
Reproductive factors
Women who have given birth at least once have a 27-31% lower risk of bladder cancer compared with those who have never given birth, meta-analyses have shown. The link is stronger in never-smokers than ever-smokers. Women who had early menopause (younger than 43-49) have a 49% increased bladder cancer risk compared with those who had menopause later, though being post-menopausal is not in itself associated with risk. Late age at menarche (older than 15) was associated with 43% decreased bladder cancer risk in a large US cohort study. Links with hormone replacement therapy (HRT) use remain unclear, while use of oral contraceptives is not associated with risk increase.
Tobacco
• Smoking
Smoking is the most important risk factor for bladder cancer. Smokers are at least 3 times as likely to get bladder cancer as nonsmokers. Smoking causes about half of the bladder cancers in both men and women.
When smokers inhale, some of the carcinogens (cancer-causing chemicals) in tobacco smoke are absorbed from the lungs and get into the blood. From the blood, they are filtered by the kidneys and concentrated in the urine. These chemicals in urine can damage the cells that line the inside of the bladder, which increases the chance of cancer developing.
• Environmental tobacco smoke
In a recent European study, exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer by almost 40%. However, the body of evidence does not support a link between ETS exposure in adults and bladder cancer risk. A record linkage study of bladder cancer incidence in the offspring of men and women diagnosed with lung cancer found a significant increase in risk of bladder cancer in those whose mothers had lung cancer, but no increased risk for paternal lung cancer. The authors interpreted this as evidence that exposure to tobacco carcinogens in utero or while breastfeeding may lead to bladder cancer in later life.
Smoking cessation after diagnosis may favourably alter the course of the disease but the evidence is incomplete. It has also been suggested that high fruit consumption may reduce the effect of smoking on developing bladder cancer.
The precise mechanism by which cigarette smoking induces bladder cancer is unclear. Studies show that risk varies by type of tobacco, with a higher risk for black ‘air-cured’ than blond ‘flue-cured’ tobacco. Smokers of black tobacco have higher reported levels of aromatic amines in their urine than smokers of blond tobacco. These aromatic amines are known urothelial carcinogens and the ability to detoxify them is compromised in people who are ‘slow acetylators’ and it is suggested that these people are at higher risk than ‘fast acetylators’ (see Molecular biology and genetics section).
Tobacco tars have been shown to induce bladder papillomas and carcinomas in mice. It is thought that prolonged exposure of the bladder to such urinary carcinogens during the excretory process may lead to the development of bladder cancer.
Workplace exposures
Certain industrial chemicals have been linked with bladder cancer. Chemicals called aromatic amines, such as benzidine and beta-naphthylamine, which are sometimes used in the dye industry, can cause bladder cancer.
Workers in other industries that use certain organic chemicals also may be at risk for bladder cancer if exposure is not limited by good workplace safety practices. The industries carrying highest risks include the makers of rubber, leather, textiles, and paint products as well as printing companies. Other workers with an increased risk of developing bladder cancer include painters, machinists, printers, hairdressers (likely because of heavy exposure to hair dyes), and truck drivers (likely because of exposure to diesel fumes).
Cigarette smoking and workplace exposures can act together to cause bladder cancer. Smokers who work with the cancer-causing chemicals noted above have an especially high risk of developing bladder cancer.
Factors shown to decrease or have no effect on bladder cancer risk
Bladder cancer risk is not increased in people who dye their hair, a meta-analysis showed. People with systemic lupus erythematosus are not associated with bladder cancer, compared with people in the general population, a meta-analysis showed.
There is limited evidence that a history of gastric ulcer increases risk.
Occupational exposures
It has been estimated that, in the UK, around 7% of bladder cancer cases in men and 2% in women are linked to occupational exposures. This proportion may be higher in countries with less-regulated industrial processes.
• Aromatic amines
In 1895 Rehn reported cases of bladder cancer in a German aniline dye factory. This led to occupational studies in other countries but it was not until the 1950s that the risk from aromatic amines, particularly benzidine and a-and ß-naphthylamine, was established by Case.
Aromatic amines were widely used in the manufacture of dyes and pigments for textiles, paints, plastics, paper and hair dyes, in drugs, pesticides and as antioxidants in the rubber industry. Production of ß-naphthylamine ceased in the UK in 1952 (its use was withdrawn from the rubber and cable industry prior to this in 1949) and in 1953 bladder cancer became, and still is, a prescribed industrial disease.
• Diesel engine exhaust
In June 2012, IARC classified diesel exhaust as associated with an increased risk of bladder cancer. This was based on limited evidence mainly from studies of highly-exposed workers.
• Polycyclic aromatic hydrocarbons (PAH)
Exposure to polycyclic aromatic hydrocarbons (PAH), which are by-products of combustion processes and therefore present in a range of industries, has also been investigated. It is calculated that about 4% of bladder cancer cases in European men are due to exposure to PAH. A recent meta-analysis showed a risk increase of about 30% for bladder cancer in painters and the International Agency for Research on Cancer classifies occupation as a painter as a cause of bladder cancer.
Personal history of bladder or other urothelial cancer
Urothelial carcinomas can form in many areas in the bladder as well as in the lining of the kidney, the ureters, and urethra. Having a cancer in the lining of any part of the urinary tract puts you at higher risk of having another tumor. The tumor can form in the same area as before, or in another part of the urothelium (lining). This is true even when the first tumor is removed completely. For this reason, people who have had bladder cancer need close, routine medical follow-up.
Race and ethnicity
Whites are about twice as likely to develop bladder cancer as African Americans. Hispanics, Asian Americans, and American Indians have slightly lower rates of bladder cancer. The reasons for these differences are not well understood.
Reproductive factors
Women who have given birth at least once have a 27-31% lower risk of bladder cancer compared with those who have never given birth, meta-analyses have shown. The link is stronger in never-smokers than ever-smokers. Women who had early menopause (younger than 43-49) have a 49% increased bladder cancer risk compared with those who had menopause later, though being post-menopausal is not in itself associated with risk. Late age at menarche (older than 15) was associated with 43% decreased bladder cancer risk in a large US cohort study. Links with hormone replacement therapy (HRT) use remain unclear, while use of oral contraceptives is not associated with risk increase.
Tobacco
• Smoking
Smoking is the most important risk factor for bladder cancer. Smokers are at least 3 times as likely to get bladder cancer as nonsmokers. Smoking causes about half of the bladder cancers in both men and women.
When smokers inhale, some of the carcinogens (cancer-causing chemicals) in tobacco smoke are absorbed from the lungs and get into the blood. From the blood, they are filtered by the kidneys and concentrated in the urine. These chemicals in urine can damage the cells that line the inside of the bladder, which increases the chance of cancer developing.
• Environmental tobacco smoke
In a recent European study, exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer by almost 40%. However, the body of evidence does not support a link between ETS exposure in adults and bladder cancer risk. A record linkage study of bladder cancer incidence in the offspring of men and women diagnosed with lung cancer found a significant increase in risk of bladder cancer in those whose mothers had lung cancer, but no increased risk for paternal lung cancer. The authors interpreted this as evidence that exposure to tobacco carcinogens in utero or while breastfeeding may lead to bladder cancer in later life.
Smoking cessation after diagnosis may favourably alter the course of the disease but the evidence is incomplete. It has also been suggested that high fruit consumption may reduce the effect of smoking on developing bladder cancer.
The precise mechanism by which cigarette smoking induces bladder cancer is unclear. Studies show that risk varies by type of tobacco, with a higher risk for black ‘air-cured’ than blond ‘flue-cured’ tobacco. Smokers of black tobacco have higher reported levels of aromatic amines in their urine than smokers of blond tobacco. These aromatic amines are known urothelial carcinogens and the ability to detoxify them is compromised in people who are ‘slow acetylators’ and it is suggested that these people are at higher risk than ‘fast acetylators’ (see Molecular biology and genetics section).
Tobacco tars have been shown to induce bladder papillomas and carcinomas in mice. It is thought that prolonged exposure of the bladder to such urinary carcinogens during the excretory process may lead to the development of bladder cancer.
Workplace exposures
Certain industrial chemicals have been linked with bladder cancer. Chemicals called aromatic amines, such as benzidine and beta-naphthylamine, which are sometimes used in the dye industry, can cause bladder cancer.
Workers in other industries that use certain organic chemicals also may be at risk for bladder cancer if exposure is not limited by good workplace safety practices. The industries carrying highest risks include the makers of rubber, leather, textiles, and paint products as well as printing companies. Other workers with an increased risk of developing bladder cancer include painters, machinists, printers, hairdressers (likely because of heavy exposure to hair dyes), and truck drivers (likely because of exposure to diesel fumes).
Cigarette smoking and workplace exposures can act together to cause bladder cancer. Smokers who work with the cancer-causing chemicals noted above have an especially high risk of developing bladder cancer.
Factors shown to decrease or have no effect on bladder cancer risk
Bladder cancer risk is not increased in people who dye their hair, a meta-analysis showed. People with systemic lupus erythematosus are not associated with bladder cancer, compared with people in the general population, a meta-analysis showed.