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Method : Literature review
Background : Urinary bladder carcinoma is one of the most prevalent tumors woldwide and smoking is one of its major risk factor ,hence studying the relationship between smoking and urinary bladder carcinoma is of great importance
Results : Relationship between smoking and urinary bladder carcinoma is not clear although recent studies has shown that it might be related to the VEGF , apoptosis , urinary ph and causes mutation in the DNA. There is equal risk between males and femlesin relation to urinary bladder carcinoma related smoking.
Results have shown that the risk of smoking is more apparent in the current smokers than non smokers and water pipe smoking has a borderline risk.
Conclusion: Smoking is a major risk factor in urinary bladder carcinoma with equal risk in males and females , cessation of smoking decreases the risk to almost normal
keywords : Smoking, urinary bladder carcinoma , risk factor , pathogenesis
literature review made by searching PubMed with following restrictions: 5 years , humans , free full article and English
Urinary bladder carcinoma is one of the most prevalent cancers worldwide, the seventh most common .In North America and Europe is considered the eleventh most common cancer (3), in Egypt it is the most common malignancy in males.(6)
Therefore studying the risk factors for Urinary bladder carcinoma is important to decrease the prevalence and incidence, risk factors include Bilhariziasis, aniline dye.
Smoking is considered one of the major risk factors for urinary bladder carcinoma .
Although the exact relationship between smoking and urinary bladder carcinoma is still unclear, smoking is one of the major and important risk factors for developing of urinary bladder carcinoma. Tobacco smoking contain a lot of the carcinogenic agents like poly cyclic aromatic hydrocarbons and aromatic amines, substances that are excreted by the kidney, known to be harmful to the urinary tract, and cause bladder cancer secondary to genetic damage.
Studies have shown that smoking increases the risk to get bladder carcinoma by 6 times and it is responsible for 50 % of bladder carcinoma , it is more prevalent in developing countries due to the diffuse spread of this ugly habit, the easiness of getting it and the laxity of the governments to fight it . (3)
After filtering of these carcinogenic gents through the urinary tract, it is stored into the urinary bladder which damages its lining epithelium and make transitional cell mutation.
Tobacco smoking is considered as the initiator for the carcinogenesis. Many proteins are showen to be a part of the angiogenesis process in the developing of carcinoma likeP53 and VEGF (vascular endothelial growth factor) which showed to be the main one in this process by increasing the vascular permeability and inducing endothelial cell migration, So the VEGF helps in the progression of the cancer, studies have shown that the degree of severity of bladder carcinoma is directly related to degree of expression of the VEGF. (4)
Studies have shown that apoptosis has higher effect in urinary bladder carcinoma related to smoking more than VEGF, apoptosis is mainly under control of P53 gene which is found to be highly mutated in urinary bladder carcinoma.(4)
Cigarette smoking increases the acidity of urine which causes compounds like Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite to be hydrolyzed, and this causes DNA damage and mutation .(1)
A recent study has shown that urine ph is not a good indicator in ex_smokers or non smokers ,while urine ph is strongly related to bladder carcinoma in current smokers , experimentally not proven by studies yet that changing urine ph that decrease the hazardous affect of smoking related to bladder carcinoma (1)
Studies showed that cigarette smoking increases the prevalence of urothelial carcinoma to 77% and sqamaeous cell carcinoma to 69% among men. Also those studies showed that the number of cigarettes smoked per day and risk of urothelial carcinoma, between years smoked and risk of urothelial carcinoma, and between pack-years and risk of urothelial carcinoma were observed. On the other hand former cigarette smokers have no relation between the number of cigarettes smoked per day and risk of urothelial carcinoma, between years smoked and risk of urothelial carcinoma, and between pack-years and risk of urothelial carcinoma.
Researches have shown that those who are smoking water pipe have borderline relationship to the urothelial carcinoma but not with the sqamaseous cell carcinoma. There was no dose-relationship between risk of urothelial carcinoma and number of hagars smoked per day, duration of smoking, or Hagar-year. Patients who have schistosomiasis and smoke have no additional risk for urinary bladder carcinoma.(2)
A study has been made in New England shown equal risk for urinary bladder carcinoma between men and woman. it also shown that pack per year and intensity of smoking have reached the plateau according to the risk but not the duration of smoking, this plateau has been observed in many cancer related smoking . Smoking for a longer time is more hazardous than heavy smoking for a shorter duration. An explanation for the observed plateau is the difference in inhalation pattern , meaning that if u inhaled less this means less exposure to carcinogens per cigarette and subsequently less damage . (5)
Scientists are still unclear about the precise pathogenesis of smoking related urinary bladder carcinoma but studies have shown that smoking increases the risk by 6 times and cause about that 50 % of all urinary bladder carcinoma with equal incidence of males and females .
Studies shown that angiogenesis plays an important role in increasing the progression of urinary bladder carcinoma by the VEGF which increases the vascular permeability and induce endothelial cell damage. The degree of expression of the VEGF is strongly related to the degree of severity of the urinary bladder carcinoma.
A lot of important compounds like Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite are hydrolyzed by the acidic urine of the smoker. Recent research showed a strong correlation between the urine ph and current smokers but there is no relation between the urine ph and the former cigarette smoker.
A study showed that number of cigarette per day, duration of smoking and smoking index have a very high effect on the risk of urinary bladder carcinoma in current smokers but they have a lesser effect on the risk in the former smokers. On the other hand water pipe smokers have a borderline risk factor for urinary bladder carcinoma. There was no dose-relationship between risk of urothelial carcinoma and number of hagars smoked per day, duration of smoking, or Hagar-year.
Longtime smoking is proved to be more dangerous than heavy smoking for shorter time in relation to urinary bladder carcinoma ,the pack per year and the interxity of smoking have reached a plateau in the risk possibly due to the differnce in the inhaltion patterns whereas the duration hasn;t reached a plateau.
In case of duration the relationship is pretty simple and obvious, the longer u smoke ,the more likely hood to get cancer, and also justified longer smoking means longer periods of carcinogenic substances to take effect
Recommendation for future research
Studies has to made to detect the exact pathogenesis of smoking on urinary bladder carcinoma.
Also research has to be made to explain the plateau observed in some research
1) Urinary pH, cigarette smoking and bladder cancer risk
2) Cancer epidemiology ,biomarkers and prevention
3) Cause–effect? Understanding the risk factors associated with bladder cancer
4) Expressional evaluation of Vascular Endothelial Growth Factor (VEGF) protein in urinary bladder carcinoma patients exposed to cigarette smoke
5) A Case – Control Study of Smoking and Bladder Cancer Risk: Emergent Patterns Over Time
6) Incidence analyses of bladder cancer in the Nile delta region of Egypt
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