Epidemiology

in the Name of GOD

UROTHELIAL TUMORSEPIDEMIOLOGY: OF THE BLADDER

M Zargham MDIsfahan University MC

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.)

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

Incidence

The incidence and prevalencerates increase with age, peaking

in the 8th decade of life,and there is a strong association

between environmentaltoxins and urothelial cancer

formation( Jemal et al, 2008;Parkin, 2008.)

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.

Incidence of genitourinary cancers in the Islamic Republic of Iran:

The prevalences ofurological cancers were as follows:

bladder cancer 48.3%; prostate cancer 33.4%renal cell carcinoma 10.3%; renal pelvis and

ureter cancer 0.75%; testicularcancer 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

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

mortalityfrom the disease increases with age .

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.

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.

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 in27% of white, 15% of African-

American, and 3% of Asian males.

External Risk Factors

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.)

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.

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

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.)

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.

Opium consumption and risk of bladder cancer: A case-control analysis

Heavy smokers with the opium consumptionexhibited 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

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.

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 andZeegers, 2008.)

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 womenAnalgesic Abuse/ Artificial Sweeterners

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 .)

InflammaInflammation/Infectiontion/InfectionInflammation/Infection

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

Radiation

Interestingly, urothelial cancerformation 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

Chemotherapy

Theonly chemotherapeutic agent

that has been proven to cause bladder cancer is cyclophosphamide,

Nilsson and Ullen, 2008

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

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.