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Bladder Cancer: Epidemiology and Pathogenesis
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== Pathogenesis == === Risk factors === === External risk factors (7): === # '''<span style="color:#ff0000">Tobacco exposure</span>''' #* '''Most common risk factor''' #** Responsible for 30-50% of all bladder cancers in males #* Relative risk 2-6x; #* Intensity and duration of smoking are linearly related to risk #** Smoking cessation reduces the risk of urothelial cancer formation #*** Former smokers still have a higher risk of bladder cancer than those who never smoked #** Current tobacco use and cumulative lifetime exposure may be associated with recurrence and progression in NMIBC #* Cigars and pipes are probably associated with bladder cancer formation, but there are few studies evaluating only cigar and pipe smokers because of the high probability that these subjects also smoke cigarettes #* The risk of second-hand smoke in bladder cancer formation is low and not statistically different from that for non-smokers # '''<span style="color:#ff0000">Occupational exposure</span>''' #* '''Second most common cause''' (5% of cases) #* '''Aromatic β-naphthylamine (most implicated as cause), amines, benzenes, arsenic, polycyclic aromatic hydrocarbons, and chlorinated hydrocarbons''' #* '''<span style="color:#ff0000">Primarily in areas with a heavy concentration of chemical industries:</span>''' #** '''<span style="color:#ff0000">Dye (Aniline dye)</span>''' #** '''<span style="color:#ff0000">Rubber</span>''' #** '''<span style="color:#ff0000">Plastic</span>''' #** '''<span style="color:#ff0000">Dry-cleaning</span>''' #** '''<span style="color:#ff0000">Paint</span>''' # '''<span style="color:#ff0000">Pelvic radiation</span>''' #* Latency period is 15 to 30 years # '''<span style="color:#ff0000">Cyclophosphamide</span>''' #* The only chemotherapeutic agent that has been proven to cause bladder cancer # '''<span style="color:#ff0000">Chronic inflammatory changes in the bladder (catheter use, stones, and recurrent infections)</span>''' #* '''Chronic infection with S. haematobium or, to a lesser degree, other bacteria leads to squamous cell carcinoma of the bladder''' #** Schistosomiasis-induced bladder cancer is more common in developing countries, such as Egypt; most common histology in these countries is still urothelial #* '''Spinal cord–injured patients are also at risk for developing squamous cell carcinoma''', most likely because of chronic catheter irritation and infection. #** '''Incidence of bladder cancer in spinal-cord injury patients <5%''' #* HPV may be associated with increased risk of urothelial carcinoma # '''<span style="color:#ff0000">Chronic phenacetin use/analgesic abuse</span>''' #* Consumptions of large quantities of phenacetin (5-15 kg during a 10-year period) or acetaminophen (the active metabolite of phenacetin) have been associated with an increased risk of renal cancer and, perhaps, bladder cancer. #** However, these studies relied on interviews and questionnaires to ascertain drug exposure rather than actual determination of analgesic use. A nested matched case-control study found no association between acetaminophen or other nonsteroidal anti-inflammatory drug ingestion and bladder cancer # '''<span style="color:#ff0000">Arsenic exposure</span>''' * '''(Diet)''' ** In general, a Mediterranean diet leads to the lowest urothelial cancer risk. A diet rich in fruits and vegetables is protective against bladder cancer formation. ** No evidence of an increased risk of bladder cancer in consumers of artificial sweeteners ** There are no clear dietary or micronutrient programs to prevent primary bladder cancer === Genetic risk factors === * '''<span style="color:#ff0000">Family history</span>''' ** '''First-degree relatives''': relative risk 2x * '''<span style="color:#ff0000">Lynch syndrome (hereditary nonpolyposis colon cancer)</span>''' ** '''See [https://test.urologyschool.com/index.php/Lynch_syndrome Lynch Syndrome] Chapter Notes''' **'''Autosomal dominant, germline mutation in mismatch repair genes''' ** '''Associated with extracolonic cancer, including bladder cancer and upper urinary tract urothelial carcinoma''' *** ≈5% of patients with LS are diagnosed with bladder cancer * Null GSTM1 and slow NAT-2 lead to high levels of 3-aminobiphenyl and higher risk of bladder cancer
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