Bladder cancer is the most common tumor of the urinary system in China, occupying the first place in both its incidence and mortality rates. Bladder cancer is the second most common genitourinary malignancy in the U.S. In 2009, approximately 70,980 people were diagnosed with bladder cancer by clinicians, including 52,810 men and 18,170 women, and approximately l,000 people die from bladder cancer each year. The development of bladder cancer is a multifactorial and multi-step process. The susceptibility factors of bladder cancer can be divided into three main areas: first, chemical and environmental exposures, such as aromatic amines, aniline dyes, nitrites and nitrates, acrolein, coal and arsenic, but the most important environmental factor is smoking; second, chronic irritation, such as long-term indwelling catheterization, schistosome infection, chronic infection and pelvic irradiation; third, genetic factors. With the increased analysis of bladder cancer population, the effects of these susceptibility factors on bladder cancer are gradually reported, and this article gives a brief introduction to the currently known susceptibility factors about bladder cancer.
Smoking Over the past 50 years, there have been numerous studies on the relationship between smoking and bladder cancer, and several case-control and prospective studies have confirmed that smoking is an important susceptibility factor for bladder cancer. Studies have shown that the risk of bladder cancer is 2.5 times higher in people who smoke than in nonsmokers, and that approximately 50% of men with bladder cancer and 35% of women with bladder cancer can be attributed to smoking. The risk of bladder cancer increases significantly with increasing daily cigarette smoking, with increasing years of smoking, and with increasing smoke inhalation depth; the risk increases with younger age of smoking initiation and increases with increasing years of smoking, number of cigarettes per day, and depth of smoking, and decreases with increasing years of smoking cessation. While there is insufficient evidence for the association between several other forms of smoking and bladder cancer, cigar smoking, pipe smoking, and passive smoking may increase the risk of bladder cancer. However, the published studies do not all agree on the relationship between the risk of developing bladder cancer and the duration of smoking cessation. Quitting smoking slows the process of tumor development, but it is controversial whether long-term smoking cessation reduces the risk of bladder cancer to non-smoking levels, but the risk of bladder cancer decreases significantly after several years of cessation. It is estimated that 30,000 of all cancer deaths in the United States would have been prevented if smoking had been stopped early.
Occupational Many industrial chemical carcinogens such as 2-naphthylamine, 4-aminobiphenyl, 4-nitrobiphenyl, benzidine, aniline dyes, coal ash, and chlorinated aliphatic compounds are thought to be associated with the development of bladder cancer. The effects of these carcinogens are often insidious and take a long time to manifest, sometimes as long as 30 to 50 years. And occupational exposure to these chemical carcinogens is the main pathway, so the incidence of bladder cancer is higher in jobs with long-term exposure to such substances, such as dyes, leather, rubber, textiles, construction, painters, truck drivers, etc. Yasunaga et al. showed that mutations in the P53 gene in these occupational bladder cancer patients were significantly different from mutations in the P53 gene in patients with non-occupational episodic bladder cancer.
Gender After excluding the effects of smoking, high-risk occupations, etc. it is still found that the incidence of bladder cancer is much higher in men than in women, about 3-4 times higher than in women. It is generally believed that risk factors such as smoking and gout may partially explain the higher incidence of bladder cancer in men than in women, but there is still no reasonable theory to explain this phenomenon. Environmental exposure and exposure to industrial chemicals were previously thought to be responsible for the difference in incidence between men and women, and some recent studies suggest that this may be related to sex hormones and their receptors. In recent years, there have been more studies on bladder cancer and prostate enlargement, considering that prostate enlargement causes urinary retention, which concentrates carcinogens in the urine and increases the contact time with the bladder mucosa, which can also lead to a higher incidence of bladder cancer in men than in women. Although the incidence rate is higher in men than in women, the difference in mortality is not as pronounced as the incidence rate, and women are more likely than men to have multifocal, larger, higher-grade bladder cancer and to have a higher chance of metastasis.
Age Age is an important independent susceptibility factor for the development of bladder cancer. Although bladder cancer can occur at any age, the prevalence of bladder cancer generally increases dramatically after the age of 70 years, reaching a peak after the age of 85 years, with some data indicating that the incidence of bladder cancer in the United States is 33/100,000 people between the ages of 65-70 years, and reaches 296/100,000 people after the age of 85 years. Patients aged >65 years are 15 times more likely to die than those aged <65 years. Current theories suggest that as patients age, their exposure to environmental and workplace carcinogens increases as does the duration of exposure, making older individuals more susceptible to bladder cancer, and that older individuals have reduced resistance and repair capacity compared to younger individuals, which increases their risk of developing bladder cancer. Chronic infection Adenoid cystitis is considered to be a precancerous lesion of bladder cancer, and its transformation into bladder cancer is a complex process that is the result of a combination of factors. However, some studies have shown that patients with adenoid cystitis accompanied by long-term chronic local irritation of the bladder mucosa, such as long-term chronic infection, bladder stones, and urinary tract obstruction, are much more likely to develop bladder cancer. Bladder stones are considered to be a high risk factor for the development of bladder cancer due to the long-term mechanical irritation of bladder stones, which can induce tumorigenesis but there is no clear evidence of the relationship between bladder stones and bladder cancer. Fluid intake Braver and Colleagues compared differences in fluid intake in different populations in relation to bladder cancer development and found that total fluid intake was negatively associated with bladder cancer risk. The mechanism may be that reduced fluid intake leads to concentrated urine and less frequent urination, which increases the exposure time of bladder epithelium to carcinogenic substances in urine and promotes the development of bladder cancer, and this hypothesis has been confirmed by animal experiments. However, the opposite view is that ingestion of excessive fluid, especially tap water treated with chlorine or beverages processed from tap water, can increase the risk of bladder cancer, and it is pointed out that ingestion of large amounts of fluid can expand the bladder, thus increasing the surface area of the bladder exposed to chemical carcinogens. Chlorine disinfection of drinking water has also been reported in China as a possible risk factor for bladder cancer. Diet Structure In recent years, there has been increasing interest regarding the effect of diet on tumors. A current study from Silberstein and Parsons showed that meat, fat, coffee, and tea can significantly increase the risk of bladder cancer, cruciferous vegetables, carrots, and fruits can reduce the possibility of bladder cancer, and vitamins A, C, E, carotenoids, and selenium may help reduce the risk of bladder cancer, but further research is needed. Schistosomiasis infection The association between schistosomiasis infection and bladder cancer has long been known, mainly in the form of increased occurrence of squamous carcinoma. Schistosomiasis is endemic in Egypt and some parts of the Middle East, and bladder cancer ranks first among cancers suffered by adults. The prevailing view is that schistosome infection can cause mutations in the P53 gene, leading to the development of bladder cancer, and there have been reports of P53 mutations in up to 96% of patients with schistosomal bladder cancer. Hair dyes Several cohort and case-control studies have found an increased risk of bladder cancer among hairdressers and colorists with occupational exposure to hair dyes and concluded that the risk of bladder cancer is much higher in those who have worked for more than 10 years than in those who have worked for less than 10 years.Andrew et al. did not find an association between personal use of hair dyes and bladder cancer based on the results of several large sample case-control and cohort studies, but by controlling for After controlling for confounding factors, regression analysis showed that hair dye use was associated with bladder cancer. They further found that hair dye use increased bladder cancer risk in women but not in men, possibly because women are more prone to aromatic amine activation. Drugs The drug with a clearer association with bladder cancer, finasteride, has been discontinued. Patients are all overdosed due to its possible carcinogenic effect of 4-vinylaminobenzene, whose chemical structure approximates that of known uroepithelial carcinogens. A recent Korean study concluded that cyclophosphamide has a clear association with bladder cancer, with a significantly higher incidence of bladder cancer in women treated with cyclophosphamide for SLE, and Monach and Arnold similarly reported that long-term cyclophosphamide use increases the incidence of bladder cancer. Phenobarbital has been reported to reduce the incidence of bladder cancer in smokers, suggesting that it may be that the liver produces some inducible enzyme in the metabolism of phenobarbital that is involved in the detoxification of bladder carcinogens, such as aminobiphenyl and naphthylamine. However, a 2003 study by Castelao showed that in the general population taking phenobarbital, they did not have a significant decrease in bladder cancer incidence. There is no epidemiological basis for the hereditary cause of the vast majority of bladder cancers. It has been reported that there is a tendency for bladder cancer to cluster in families, and that people with grandparents who have bladder cancer have a higher incidence than others.