Bladder cancer risk factors
This page presents information on the risk factors for bladder cancer including by tobacco, occupation exposure, hair dyes, medicines and medical conditions, hormonal factors, family history and food and drink. Overall, it has been estimated that, in the UK, around 44% of bladder cancer cases in men and 37% in women are linked to lifestyle and environmental factors. The proportion is higher in men than women due to higher rates of smoking in men in the past, and higher exposure to occupational hazards among men.1
Smoking cigarettes is the principal preventable risk factor for bladder cancer in both men and women. A study published in December 2011 estimated that 38% of bladder cancer cases in men and 34% in women in the UK in 2010 were caused by smoking.2
Current smokers have up to four times higher bladder cancer risk compared with never-smokers, a cohort study of people aged 50 and over showed,75 with the highest risks for people smoking for the longest, or smoking a greater amount of cigarettes each day.70-71
Smoking cessation reduces risk, but risk in ex-smokers remains higher than never-smokers for more than 20 years.70-71
In a recent European study, exposure to environmental tobacco smoke (ETS) during childhood increased the risk of bladder cancer by almost 40%.4 However, the body of evidence does not support a link between ETS exposure in adults and bladder cancer risk.49 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.5
Smoking cessation after diagnosis may favourably alter the course of the disease but the evidence is incomplete.6 It has also been suggested that high fruit consumption may reduce the effect of smoking on developing bladder cancer.7
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.8 Smokers of black tobacco have higher reported levels of aromatic amines in their urine than smokers of blond tobacco.9 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).10
Tobacco tars have been shown to induce bladder papillomas and carcinomas in mice.11 It is thought that prolonged exposure of the bladder to such urinary carcinogens during the excretory process (Figure 4.1) may lead to the development of bladder cancer.
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section updated 01/03/06
Bladder cancer was one of the first cancers shown to be industrially associated and has an important place in the history of occupational disease.
In 1895 Rehn reported cases of bladder cancer in a German aniline dye factory.12 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.13
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.14 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)15 and in 1953 bladder cancer became, and still is, a prescribed industrial disease.16
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.17 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.66,69
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.72
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.64,68 This proportion may be higher in countries with less-regulated industrial processes.
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Within the EU, the Scientific Committee on Cosmetic Products and Non-food Products (SCCNFP) is establishing a system for the regulation of hair dye substances.44
Contrary to previous research, a recent study in Sweden showed no increase in bladder cancer among hairdressers in recent decades and suggested that modern hair dyes are not carcinogenic.18
Personal use of hair dyes has also been studied with conflicting results The SCCNFP’s strategy is to require the industry to provide safety dossiers for all dye precursors and dyes for permanent and semi-permanent hair dye formulations and then to evaluate these with the aim of setting up a ‘positive list’ of hair dyes.45-48
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section updated 01/03/06
A very small proportion of bladder cancer cases are associated with therapeutic irradiation in the pelvic region, for example for testicular cancer21 or cervical cancer.22 Men with a history of prostate cancer, both those treated with and without radiotherapy, have an increased risk of bladder cancer.23-25 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.50
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.67
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.26
One study showed a doubling in risk of bladder cancer in patients with condylomata acuminata (genital warts).60 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.61
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The risk of bladder cancer is up to around a third higher in diabetics than non-diabetics, several meta-analyses have shown.76-79,86 Diabetes treatment is likely to explain much of this increased risk, though treatment type often relates to diabetes stage, which may further confound findings. Type II diabetics treated with pioglitazone (a type of thiazolidinedione) have around a 20% higher bladder cancer risk compared to those not receiving the drug, meta-analyses of observational studies show.80-82,87 This risk appears to increase with cumulative dose and duration of exposure.87 In randomised control trials the risk may be 2.5 times higher in diabetic pioglitazone users versus diabetic non-users.87 However, there appears to be no association between other thiazolidinediones (specifically rosiglitazone) and bladder cancer risk.81,82,87
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section updated 28/02/14
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.83,84 The link is stronger in never-smokers than ever-smokers.84 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.83 Late age at menarche (older than 15) was associated with 43% decreased bladder cancer risk in a large US cohort study.85 Links with hormone replacement therapy (HRT) use remain unclear, while use of oral contraceptives is not associated with risk increase.83-85
section reviewed 05/12/13
section updated 05/12/13
Higher intake of fruit has been associated with a small but significant reduction in the risk of bladder cancer. An increase in fruit consumption of 100 grams a day is estimated to reduce risk by approximately 20%.32-34 However, some studies have shown no association with fruit intake and it is not possible to say there is a definite protective association.56-58
Two Chinese cohort studies have reported a significant increase in risk with higher consumption of soya foods.35,36 This association is not clearly understood: one theory is that the chemical reaction of chlorine in water with humic substances in beans during fermentation may act as a bladder carcinogen.
Results of a pooled analysis of 10 European studies show that heavy coffee consumption (more than 10 cups per day) is associated with a significantly increased risk of bladder cancer in men and women37 but there is no evidence of risk increase with moderate consumption.38,39
The body of evidence indicates that overall fluid consumption does not affect bladder cancer risk.34 Some studies have shown that high tap water consumption increases risk of bladder cancer, which may be linked to chlorination.41 However, three studies have shown a lower risk of bladder cancer with higher water consumption, particularly among people who urinate frequently.59,62, 63A meta-analysis has reported a significant risk ratio of 1.4 for having a chlorinated water supply.42 In another pooled analysis, having a water supply containing high levels of trihalomethanes (by-products of chlorination) was associated with a significant risk increase in men but not women.43
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Schistosomiasis is a parasitic infection that occurs throughout Africa and the Middle East. One form of the parasite, schistosoma haematobium, is linked to bladder cancer and was estimated to cause around 10,600 cases of the disease worldwide in 2002.65
section reviewed 01/03/06
section updated 01/03/06
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