1. Epidemiology in the Name of GOD

2. M Zargham MD Isfahan University MC

3. Global Burden of Bladder Cancer  Bladder cancer is the 9th most common cancer worldwide, with 357,000 cases recorded in 2002  Bladder cancer is the 13th most common  cause of death, accounting for 145,000 deaths worldwide  (Ferlayet al, 2007; Parkin, 2008).

4. There is a geographic difference in bladder cancer incidence rates across the world with the highest occurring in Southern and Eastern Europe parts of Africa, the Middle East, and North America and the lowest occurring in Asia and underdeveloped areas in Africa

5. Incidence  The incidence and prevalence  rates increase with age, peaking in the 8th decade of life,  and there is a strong association between environmental  toxins and urothelial cancer formation  (Jemal et al, 2008;Parkin, 2008).

6. incidence  Unfortunately, the incidence rate is rising the  fastest in underdeveloped countries where industrialization has  There has been a 5% decrease in bladder cancer mortality from  1990 to 2004 despite a continued rise in the incidence of  the disease.

7. Incidence of genitourinary cancers in the Islamic Republic of Iran:  The prevalences of  urological cancers were as follows:  bladder cancer 48.3%; prostate cancer 33.4%  renal cell carcinoma 10.3%; renal pelvis and ureter cancer 0.75%; testicular  cancer 6.15%; penile cancer 0.15%; urethral cancer 0.45%  Akbari ME, Hosseini SJ, Rezaee A,... Asian Pac J Cancer Prev. 2008 Oct-Dec;9(4):549-52

8. Gender  Bladder cancer is 3 times more common in men than in women  The median age of bladder cancer diagnosis is 70 years of age for men and women, and the incidence and mortality  from the disease increases with age.

9. incidence rate  The incidence rate of bladder cancer is decreasing faster in men than in women because of the recent decrease in the  percent of men smoking compared with women.

10. Etiology  Bladder cancer is caused by genetic abnormalities and external risk factors, including carcinogen exposure, nutritional factors, fluid  intake, alcohol, inflammation, infection, chemotherapy, radiation,  and possibly artificial sweeteners.

11. Genetic:  The null GSTM1 and slow NAT-2 lead to high levels of 3-aminobiphenyl and higher  risk of bladder cancer.  These polymorphisms are present in  27% of white, 15% of African-American, and 3% of Asian males.

12. External Risk Factors

13. Environmental Risk Factors  In addition to the skin and lungs, the bladder is the main internal  organ affected by occupational carcinogens. The primary culprits  are the aromatic amines that bind to DNA  ( Delclos and Lerner, 2008; Reulen et al, 2008).

15. Agriculture workers having the lowest and rubber workers the highest risk of bladder cancer formation.  Environmental carcinogens can enter the system and cause bladder cancer from inhalation or through skin absorption. In general, there is a long latency period of 10 to 20 year.

16. Smoking  Tobacco is the main known cause for urothelial cancer formation,particularly cigarette smoking, accounts for 60% and 30% of all urothelial cancers in males and females, respectively

17. Smoking  Overall there is a 2- to 6-times greater chance of developing urothelial cancer with smoking, and the intensity and duration of smoking is linearly related to the  increased risk, with no clear plateau level  (Brennan et al,2000; Smoke, 2004; Boffetta, 2008).

18. Prominent bladder cancer risk factors in Iran.  Among life style factors,  cigarette smoking  opium use  history of excessive analgesic use and  hair dye use had significant correlations with BC  Asian Pac J Cancer Prev. 2010;11(3):601-  Shakhssalim N, Hosseini SY, Basiri A, Eshrati B,…UNRC.

19. Opium consumption and risk of bladder cancer: A case- control analysis  Heavy smokers with the opium consumption  exhibited a 6-fold elevated risk for BC  When stratified according to different grades of BC, a 3.4-fold increased risk was associated with the opium consumption in grade III  Hosseini SY, Safarinejad MR, Amini E, Urol Oncol. 2010 Nov- Epub 2008 Dec 25 Dec

20. A diet rich in fruits and vegetables is protective against bladder cancer formation.  However, even if not directly causative,  there is a very clear association between a healthy diet and a decreased risk of urothelial cancer formation.

21. Fluid Intake  A meta-analysis concluded that approximately  50% of the studies on fluid intake and bladder cancer risk showed  an association and 50% did not find an association  (Brinkman and  Zeegers, 2008).

23. Alcohol?  However, a meta-analysis of available literature from the last 20 years did not show an association between alcohol intake  and bladder cancer, with a relative risk of 1.2 overall—1.3 in men and 1.0 in women Analgesic Abuse/ Artificial Sweeterners

24. Bacterial infection.  Several investigators have suggested that chronic bacterial  infections may play a role in bladder cancer formation  National Bladder Cancer Study Group reported a 4.8 relative risk (CI, 1.9 to 11.5) of bladder cancer formation for subjects with greater than or equal to three urinary tract infections versus none  (Kantor et al, 1984).

25. InflammaInflammati on/Infection tion/Infection Inflammation/Infecti on  Infection is clearly a contributor to the formation of squamous  cell carcinoma in patients chronically infected with Schistosoma hematobium and will be covered in the section on squamous cell  carcinoma of the bladder  (Abol-Enein, 2008). Inflammation/Infection

26. Radiation  Interestingly, urothelial cancer  formation after radiation is not age related, but the latency period is 15 to 30 years. Further support that radiation can cause bladder cancer is an increased risk  of urothelial cancer in those patients with prostate or cervical cancer who were treated with radiation therapy

27. Chemotherapy  The  only chemotherapeutic agent that has been proven to cause bladder cancer is cyclophosphamide,  Nilsson and Ullen, 2008

28. Heredity  First-degree relatives of patients with bladder cancer have a twofold increased risk of developing urothelial cancer themselves, but high-risk of urothelial cancer families are relatively rare  (Aben et al, 2002; Murta-  Nascimento et al, 2007; Kiemeney, 2008

29. hereditary  There is a component to bladder cancer formation,probably through low-penetrance genes (NAT-2 and the GSTM1 polymorphisms) that increase the susceptibility  of carcinogens.