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Bladder cancer risk factors

The key risk factors for bladder cancer are discussed on this page. Bladder cancer risk is also strongly linked with age and sex.

Around 42% of bladder cancers in the UK are linked to lifestyle: 44% in males and 37% in females.1

Meta-analyses and systematic reviews are cited where available, as they provide the best overview of all available research and often take study quality into account. Individual case-control and cohort studies are reported where such aggregated data are lacking.

 

Bladder cancer risk factors overview

The International Agency for Research on Cancer (IARC) evaluates evidence on the carcinogenic risk to humans of a number of exposures including tobacco, alcohol, infections, radiation, occupational exposures, and medications.2The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) evaluates evidence for other exposures including diet, overweight and obesity, and physical exercise.3 IARC and WCRF/AICR evaluations are the gold standard in cancer epidemiology. IARC and WCRF/AICR’s conclusions about bladder cancer risk factors are shown in Table 4.1.

Table 4.1: IARC and WCRF/AICR Evaluations of Bladder Cancer Risk Factors

Increases risk ('sufficient' or 'convincing' evidence) May increase risk ('limited' or 'probable' evidence) Decreases risk ('sufficient' or 'convincing' evidence) May decrease risk ('limited' or 'probable' evidence)
  • Aluminium production
  • 4-Aminobiphenyl
  • Arsenic and inorganic arsenic compoundsa
  • Auramine production
  • Benzidine
  • Chlornaphazine
  • Cyclophosphamide
  • Magenta production
  • 2-Naphthylamine
  • Painting
  • Rubber production industry
  • Schistosoma haematobium
  • Tobacco smoking
  • ortho-Toluidine
  • X-radiation, gamma-radiation
  • 4-Chloro-ortho-toluidine
  • Coal-tar pitch
  • Coffee
  • Dry cleaning
  • Engine exhaust, diesel
  • Hairdressers and barbers (occupational exposure)
  • Pioglitazone
  • Printing processes
  • Soot
  • Textile manufacturing
  • Tetrachloroethylene
   

a Arsenic in drinking water is classified by WCRF/AICR as a possible cause of bladder cancer based on limited-suggestive evidence

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Tobacco

Smoking

Tobacco smoking is classified by IARC as a cause of bladder cancer (Table 4.1).2 An estimated 37% of bladder cancers in the UK are linked to tobacco smoking.1

Bladder cancer risk is 3.8 times higher in current smokers compared with never-smokers, a meta-analysis of cohort studies showed.4 Bladder cancer risk increases with amount and duration of smoking, a meta-analysis and pooled analyses of case-control studies have shown.5,6,7

Bladder cancer risk is 73-80% lower in ex-smokers who quit 25 years previously, compared with ongoing smokers, pooled analyses have shown; however ex-smokers risk remains higher than never-smokers risk.6,7

Higher bladder cancer risk in smokers may partly reflect mutual confounding by occupational exposures.8

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Occupational exposures

The following occupational exposures are classified by IARC as causes of bladder cancer (Table 4.1).2 An estimated 5-6% of bladder cancers in the UK are linked to occupational exposures.1,9

Higher bladder cancer risk in certain occupations may partly reflect mutual confounding by smoking.8

Aromatic amines

Aromatic amines are used in production of dyes, rubber, and textiles; they are also found in pesticides.9

Working in production of auramine or magenta dyes, and exposure to 4-Aminobiphenyl, benzidine, 2-Naphthylamine, or ortho-Toluidine (chemicals used in dye production), are classified by IARC as causes of bladder cancer; 4-Chloro-ortho-toluidine is classified as a probable cause (Table 4.1).2 Working in rubber production is classified by IARC as a cause of bladder cancer.2 Working as a hairdresser/barber, printer, or textile manufacturer (occupations which may involve aromatic amine exposure) is classified by IARC as a probable cause of bladder cancer, based on limited evidence.2

An estimated 1% of bladder cancers in males and females in Britain are linked to aromatic amines.9 An estimated 0.1% of bladder cancers in males and 0.3% in females in Britain are linked to working as a hairdresser/barber.9

Bladder cancer risk is 29% higher in rubber workers compared with the general population, a meta-analysis showed.14

Bladder cancer risk is 30-35% higher in hairdressers compared with the general public, meta-analyses have shown; however it remains unclear whether this is limited to hairdressers working before some carcinogenic chemicals were banned from hair dyes in the 1970s.10,11 This is distinct from domestic personal hair dye use.

Bladder cancer risk is 27% higher in leather workers compared with the general population, a meta-analysis showed.14

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Polycyclic aromatic hydrocarbons (PAH)

Polycyclic aromatic hydrocarbons (PAHs) are formed during combustion of fossil and carbon-containing fuels such as wood, coal, diesel, and fat.9

Working in aluminium production (which involves PAH exposure) is classified by IARC as a cause of bladder cancer (Table 4.1).2 Occupational exposures to coal-tar pitch, soot, or diesel engine exhaust are classified by IARC as probable causes of bladder cancer, based on limited evidence.2

An estimated 0.1% of bladder cancers in males and 0.04% in females in Britain are linked to PAHs.9 An estimated 1% of bladder cancers in males and 0.2% in females in Britain are linked to diesel engine exhaust.9

Bladder cancer risk is not associated with working in aluminium or iron and steel production, a meta-analysis showed; however there was a suggestion of increased risk.12

Bladder cancer risk is 8% higher among professional drivers and railroad workers, a meta-analysis of cohort studies showed.13 Case-control studies indicate a higher risk increase, but also that this risk increase has lessened over time.14,13

Bladder cancer risk is 31% higher in miners compared with the general population, a meta-analysis showed.14

Bladder cancer risk is 21-27% higher in mechanics compared with the general population, a meta-analysis showed.14

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Working as a painter

Working as a painter is classified by IARC as a cause of bladder cancer (Table 4.1).2

An estimated 1% of bladder cancers in males and 0.1% in females in Britain are linked to working as a painter.9

Bladder cancer risk is 28% higher in painters compared with the general population, a meta-analysis showed.15

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Arsenic and inorganic arsenic compounds

Exposure to arsenic or inorganic arsenic compounds is classified by IARC as a cause of bladder cancer (Table 4.1).2 Arsenic in drinking water is classified by WCRF/AICR as a possible cause of bladder cancer based on limited-suggestive evidence (Table 4.1).3

Bladder cancer risk is higher in people with 10μg/L or higher arsenic concentration in their drinking water, a meta-analysis showed; risk increases with higher concentrations.16 Bladder cancer risk is only increased with high-level, long-term arsenic exposure;17 an interaction with tobacco use is possible.18

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Tetrachloroethylene (PCE)

Exposure to trichloroethylene (PCE) is classified by IARC as a probable cause of bladder cancer, based on limited evidence (Table 4.1).2 PCE is used in dry cleaning fluid; working as a dry cleaner is also classified by IARC as a probable cause of bladder cancer.2

Bladder cancer risk is not associated with occupational PCE exposure, a meta-analysis showed.19 Bladder cancer risk is probably not associated with working as a dry cleaner, a meta-analysis showed; smoking may explain any apparent link.19

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Mineral oils

Mineral oils are not specifically classified by IARC as a cause of bladder cancer, however aluminium production is classified as a cause of bladder cancer (Table 4.1),2 and this, along with other metalworking, may involve exposure to mineral oils.9

An estimated 4% of bladder cancers in males and 0.7% in females in Britain are linked to mineral oils.9

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Previous cancer

Bladder cancer risk is higher in survivors of larynx,20 lung,20,21 head and neck,20,21 prostate,20,21,22 testicular,23 cervical,24 and kidney cancers,20 cohort studies have shown.

Genitourinary cancer risk is 1.7-2.7 times higher in children and TYAs who had any type of cancer in childhood, compared with the general population, a cohort study showed.25

Bladder cancer risk is probably increased in cancer survivors due to the effects of radiotherapy or chemotherapy treatment, and shared risk factors with the first cancer, including smoking.

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Ionising radiation

X radiation and gamma radiation are classified by IARC as causes of bladder cancer (Table 4.1).2 An estimated 3% of bladder cancers in the UK are linked to ionising radiation, mainly diagnostic radiation.1

Bladder cancer risk is not associated with radioactive iodine treatment for previous thyroid cancer, a meta-analysis showed.26

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Medical conditions and treatments

Chemotherapy

Chlornaphazine (a Hodgkin lymphoma treatment used in the 1950s) is classified by IARC as a cause of bladder cancer (Table 4.1).2

Cyclophosphamide is classified by IARC as a cause of bladder cancer (Table 4.1).2

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Spinal cord injury

Bladder cancer risk is higher in people with spinal cord injury, which may be due to indwelling urinary catheters, urinary tract infections or bladder calculi.27 1% of spinal cord injury patients with indwelling catheter develop bladder cancer, a meta-analysis showed.28

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Systemic sclerosis

Bladder cancer risk in women is twice higher in systemic sclerosis patients compared with the general population, a meta-analysis showed.29 Bladder cancer risk in men is not associated with systemic sclerosis.29 The risk increase may be due to use of cyclophosphamide for systemic sclerosis treatment.29

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Crohn's disease

Bladder cancer risk is twice higher in people with Crohn’s disease, versus the general population, a meta-analysis showed.30

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Diabetes

Pioglitazone (a diabetes treatment) is classified by IARC as a probable cause of bladder cancer, based on limited evidence (Table 4.1).2

Bladder cancer risk is up to around a third higher in diabetics compared with non-diabetics, meta-analyses have shown.31,32,33,34,35 This is mainly due to diabetes treatment, though treatment type often relates to diabetes stage, which may further confound findings.

Bladder cancer risk among diabetics is 20% higher in pioglitazone users versus non-users, meta-analyses of observational studies have shown; meta-analysis of randomised controlled trials (RCTs) indicates a stronger risk increase.36,37,38,39

Bladder cancer risk among diabetics is decreased or not associated with other diabetes medications.

Bladder cancer risk in men is 10% higher in those with metabolic syndrome (characterised by overweight/obesity, ineffective insulin use, diabetes and hypertension), versus those without the condition, a meta-analysis showed.40 Bladder cancer risk in women is not associated with metabolic syndrome.40

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Infections

Human papillomavirus (HPV)

Bladder cancer risk is up to 2.8 times higher in people with human papillomavirus (HPV) infection, versus uninfected people, a meta-analysis showed.41,42

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Schistosomiasis

Schistosoma haematobium infection (schistosomiasis) is classified by IARC as a cause of bladder cancer (Table 4.1).2

In Sub-Saharan Africa, Egypt, Sudan, and Yemen (schistosomiasis is essentially confined to less-developed world regions), at least 41-42% of people with bladder cancer have schistosomiasis.43

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Immune system

Organ transplant

Bladder cancer risk is around 3 times higher among renal transplant recipients, compared with the general public, a meta-analysis showed.44

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Family history and genetic conditions

Family history

Bladder cancer risk is 1.8 times higher in people with a first-degree relative (parent, sibling, child) with the disease, compared with the general population, a cohort study showed.45 Shared smoking habits are thought to explain much of this association; bladder cancer risk is also higher in spouses of people with the disease, and people with a family history of other smoking-related cancers.45,46

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Diet

Coffee

Coffee is classified by IARC as a probable cause of bladder cancer, based on limited evidence (Table 4.1).2

Bladder cancer risk is not associated with coffee intake, meta-analyses of cohort studies have shown;47,48 though meta-analyses of case-control studies indicate a possible risk increase.48,49

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Tap water

Bladder cancer risk in men may be higher in those who drink the most tap water, meta-analyses have shown.50,51 Bladder cancer risk in women is not associated tap water intake.50,51

The association may reflect the effect of tap water chlorination.50,51,52

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Overweight and obesity

Bladder cancer risk is 9% higher in obese (body mass index [BMI] 30+) people compared with healthy-weight people, a meta-analysis showed.53 However, the association may be limited to males, and residual confounding by smoking is probable, a cohort study showed.54

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Factors shown to decrease or have no effect on bladder cancer risk

Decrease

Milk is classified by WCRF/AICR as possibly protective against bladder cancer, based on limited-suggestive evidence.3

Bladder cancer risk is not associated with milk intake in studies of European populations, meta-analyses have shown.55,56,57,58

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Bladder cancer risk is lower in people with the highest versus lowest levels of the following factors, meta- and pooled analyses or systematic reviews have shown:
• Physical activity – 15% lower risk for the most versus least physically active people.59
• Giving birth – 27-31% lower risk in parous versus nulliparous women; effect stronger in never-smokers versus ever-smokers.60,61
• Later menopause – 49% lower risk in oldest versus youngest age at menopause.60
• Later menarche – 43% lower risk with menarche aged 15+ versus younger.62
• Selenium (blood or toenail levels) – 39% lower risk.63

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No effect

WCRF/AICR make no judgment on the association between bladder cancer risk and intake of cereals (grains) and their products; vegetables; fruits; no conclusion pulses (legumes); meat; poultry; fish; eggs; total fat; butter; dietetic foods; soft drinks; diet drinks; fruit juices; coffee; tea; caffeine; alcohol; chlorinated surface water; total fluid intake; sweeteners; frying; carbohydrate; protein; vitamin A; folate; vitamin C; vitamin E; multivitamin supplements; selenium; beta-carotene; alpha-carotene; lycopene; betacryptoxanthin; lutein; zeaxanthin; flavonoids; physical activity; body fatness; or energy intake, due to limited evidence.3

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Bladder cancer risk is not associated with the following factors, meta- and pooled analyses or systematic reviews have shown:

  • Environmental tobacco smoke.64
  • Alcohol.64
  • Personal hair dye use.66
  • Waterpipe smoking.67

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  • Systemic lupus erythematosus.68
  • Rosiglitazone (among diabetics).37,38,39
  • Metformin (among diabetics).69,70
  • Insulin (among diabetics), though some evidence of decreased risk.71,72
  • Paracetamol.73
  • Aspirin.73,74
  • Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) (some evidence of risk decrease in non-smokers).73,74
  • Statins.75
  • Postmenopausal hormone replacement therapy (HRT) (some evidence of risk decrease with combined oestrogen-progesterone HRT).60,61,62
  • Oral contraceptives.60,61,62

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  • Total fluid intake (some evidence of risk decrease in Asian populations, and women76).77  
  • Citrus fruits (some evidence of risk decrease in case-control studies).78
  • Sweetened carbonated beverages.79
  • Dietary folate (some evidence of risk decrease in case-control studies).80
  • Eggs.81
  • Tea (some evidence of risk decrease).77,82,83
  • Cruciferous vegetables (some evidence of risk decrease in case-control studies).84
  • Fish.85
  • Meat (some evidence of risk increase with red meat).86
  • Vitamin A (some evidence of risk decrease in case-control studies).87

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Updated: 27 October 2014