Cancer Research UK : Bladder Cancer risk factors

Bladder Cancer risk factors

This page presents information on the risk factors for bladder cancer including by tobacco, occupational exposures, hair dyes, medicines and medical conditions, hormonal factors family history and food and drink.

Tobacco and bladder cancer risk

Smoking cigarettes is the principal preventable risk factor for bladder cancer in both men and women. In Europe it is estimated that up to half the bladder cancer cases in men and a third in women are caused by cigarette smoking.1,2

Current smokers have around three times the risk of never-smokers of developing bladder cancer while ex-smokers have double the risk of never-smokers.1-3 Risk is positively associated with both increasing dose and duration of smoking.3

Smoking cessation reduces risk by 30-60 per cent, but risk in ex-smokers remains higher for more than 20 years.1,2

Passive smoking may also increase risk. In a recent European study, exposure to environmental tobacco smoke (ETS) during childhood (but not adulthood) increased the risk of bladder cancer by 40%.4 Another study showed a three-fold increased risk of bladder cancer in women heavily exposed to ETS in childhood, although no association for men. This study showed an even higher five-fold risk increase for women most heavily exposed to ETS throughout their lifetime.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 interpret 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.

Figure 4.1: Diagram of the male urinary tract

Occupational exposure and bladder cancer risk

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

Altogether it is estimated that between 5 and 10% of male bladder cancer cases in Europe are caused by occupational exposure. This proportion may be higher in countries with less-regulated industrial processes.

Hair dyes and bladder cancer risk

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

Occupational studies of hairdressers and barbers have reported elevated risks for bladder cancer but a recent study in Sweden showed no increase 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

Medicines and medical conditions and bladder cancer risk

In addition to aromatic amines, there are other established bladder carcinogens including phenacetin and certain cancer chemotherapeutic agents including cyclophosphamide.19, 20

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. Among women treated with radiotherapy the risk increased with years since treatment, to almost six-fold for women treated for cervical cancer 40 or more years previously.50

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

There is some evidence that diabetics have an increased risk of bladder cancer, with risk ratios of 2-3 reported27-29 and limited evidence that a history of gastric ulcer increases risk.30, 31 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

Hormonal factors and bladder cancer risk

Two cohort studies show a 50-75% increase in risk of bladder cancer in women undergoing menopause before the age of 47 compared to at 48 or later.51, 52 Women who have had a bilateral oophorectomy have a 60% increased risk.51

Family history and bladder cancer risk

Most studies show a two-six-fold increased risk of bladder cancer in first-degree relatives of bladder cancer patients, with a higher risk if the relative was diagnosed before the age of 45.53-55

Food and drink and bladder cancer risk

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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