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Bladder cancer (1/7): Definition, Epidemiology, and Etiology
Review Literature: EAU guidelines: superficial bladder cancer (Babjuk et al, in 2008 and 2013). Advanced bladder cancer (Stenzl et al, 2009 and Witjes et al, 2013).
- Bladder cancer (1/7): Definition, epidemiology and etiology
- Bladder cancer (2/7): Pathology
- Bladder cancer (3/7): Symptoms and diagnostic work-up
- Bladder cancer (4/7): Overview of treatment options
- Bladder cancer (5/7): Treatment of superficial bladder cancer
- Bladder cancer (6/7): Treatment of invasive bladder cancer
- Bladder cancer (7/7): Chemotherapy of metastasis
Bladder cancer is a malignant tumor that originates from the epithelial cells of the urinary bladder.
Epidemiology of bladder Cancer
- Second most common tumor of the urogenital tract
- Life-time prevalence (up to age of 75 years) is 2-3% for men and 0.5-1% for women.
- Incidence in the European Union: 27 per 100,000 for men and 6 per 100,000 for women
- Annual incidence in Germany 15,000 people.
- Mortality in the EU: 8 per 100,000 for men and 3 per 100,000 for women.
- Cancer statistics: incidence 5th position in men 11th position in women. The incidence is increasing (30% in 15 years).
- Mean age at diagnosis: 65 years. Less than 1% of bladder cancers occur in patients less than 40 years.
- 70% have superficial bladder cancer at diagnosis, 30% present with local advanced tumor with an infiltration of the tunica muscularis. 15% of patients are already metastasized.
Etiology and Pathogenesis of Bladder Cancer
Review literature: (Kalble, 2001) (Leppert et al, 2006) (Plná and Hemminki, 2001).
Smoking and Bladder Cancer:
Smoking increases the risk for bladder cancer three to fourfold. In Europe, about half of urothelial carcinomas in men and one-third in women are attributable to smoking. Smokers and ex-smokers do more often experience tumor recurrence after treatment of superficial bladder compared with non-smokers (Lammers et al, 2011).
Occupations with exposure of risk factors for bladder cancer are: chemical industry processing paint, metal or petrolium products, steel industry, auto mechanics, leather industry and dental technicians. Identified risk factors aromatic amines, polycyclic aromatic hydrocarbons and chlorinated hydrocarbons. Urothelial carcinoma is a recognized occupational disease, if there has been sufficient exposure and a reasonable latency period. In Europe, up to 10% of bladder cancers are caused by occupational exposure. In developing countries figures of bladder carcinoma are rising due to increased occupational exposure without safety guidelines.
Fluid Intake and Bladder Cancer:
A fluid intake of more than 2.5 l results in a halving of the risk for bladder cancer compared to a intake of less than 1.3 l. An increased fluid intake is especially protective for smokers. Coffee or alcohol are not risk factors for bladder cancer (Michaud et al 1999).
Nutrition and Bladder Cancer:
A healthy nutrition rich of fruits and vegetables (e.g. Mediterranean diet) lowers the risk for bladder cancer. Sweeteners were suspected to be a risk factor for bladder cancer, but modern studies did not find any evidence for an relationship.
Drugs and Bladder Cancer Risk:
Cyclophosphamide has been proven to cause bladder cancer. The causal relationship of Phenacetin and other NSAIDs to cause bladder cancer has been disputed. Chinese herbs (especially weight-reducing tablets containing Aristolochia fangchi) are supposed to be a risk factor.
Chronic Urinary Tract Infection and Bladder Cancer:
Chronic urinary tract infection (over years) is a risk factor to cause a squamous cell carcinoma of the bladder (e.g. patients with schistosomiasis, chronic catheter use).
Molecular Biology of Bladder Cancer:
The following genetic changes increase the risk of bladder cancer or correlate with tumor stage:
Activity of N-acetyltransferases (NAT1 and NAT2):
N-acetyltransferases are important for the inactivation and elimination of nitrosamines. Slow enzyme activity of N-acetyltransferases carries a higher risk of developing bladder cancer, since environmental factors causing bladder cancer are slower inactivated. The epidemiological relationship is particular prominent in patients with a smoking history.
Oncogenes and tumor suppressor genes:
Increased expression of oncogenes: wie RAS, FGFR oder p21. Tumor suppressor genes (Deletion oder mutations with or loss of action): p53, retinoblastoma gene RB1.
The loss of the long arm of chromosome 9 is detectable in all stages of bladder cancer. In advanced tumors, the loss of the short arm of chromosome 11 and 17 can be detected.
Further molecular changes of bladder cancer:
FGF receptor mutations, increased expression of laminin receptors, increased secretion of type IV collagenase and autocrine motility factor, increased expression of EGF receptors.
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