1. TOBACCO AND UROGENITAL CANCER
Mini Lecture 4
Module: Tobacco Effects and Neoplasia

2. Objectives of the Mini Lecture
GOAL OF MODULE: Provide students with an understanding of the potential threat of  cancer in different parts of the body as a result of tobacco use.
LEARNING OBJECTIVES: 
Learners will be able to:
Understand the different carcinogens in cigarette smoke and the mechanism of carcinogenesis.
Gain an overview of how smoking causes lung cancer.
Discuss how tobacco is a risk factor for digestive cancers.
Determine the types of urogenital cancer associated with smoking.
Understand the adverse effects of smoking on cancer management and the critical importance of tobacco cessation.

3. Contents Core Slides Optional Slides
Tobacco and Risk of Urogenital Cancers
Tobacco and Bladder Cancer
Tobacco Kidney Cancer
Cessation and Bladder Cancer
Tobacco and Urogenital Cancers: Mechanism

4. CORE SLIDES Tobacco and Urogenital Cancer Mini Lecture 4
Module: Tobacco Effects and Neoplasia

5. Tobacco and Risk of Urogenital Cancers
Smoking increases the risk of cancers of the uterine cervix, urinary bladder, and penis.1
Use of tobacco is a significant risk factor for penile carcinoma; the use of more than one form of tobacco increases this risk.1
Notes:
Studies conducted in South India reveal that the average annual age-adjusted incidence of penile cancer is 2.9 per population. All forms of tobacco use were found to be significant risk factors for penile carcinoma. A clear dose-response relationship for smoking and chewing was observed, although it was not possible to differentiate between the effect of areca nut and tobacco. Accumulation of carcinogens in smegma may be an important factor.1 Cigarette smoking was associated with bladder cancer among male and female smokers, and showed a significant dose- and time-response relationship for both sexes.
References:
Harish K, Ravi R. The role of tobacco in penile carcinoma. Br J Urol. 1995; 75(3):375-7.
1. Harish and Ravi 1995

6. Tobacco and Bladder Cancer
Cigarette smoking—Most important risk factor for bladder, renal pelvis, or ureter cancers.1
Exposure to SHS during childhood increased the risk of bladder cancer by 40%2 and 5-fold increased risk for women heavily exposed to SHS.3
Smokers have 1.5–3 times risk of developing bladder cancer as non smokers.1
There is a dose–response relationship with both number of cigarettes smoked and duration of cigarette smoking and risk of developing bladder cancer.1
Notes:
Smokers of black (air-cured) tobacco are likely to be at higher risk of bladder cancer than smokers of blond (flue-cured) tobacco, and this factor is likely to explain much of the high incidence rates observed in Spain, Italy, and Uruguay, where smoking of black tobacco was common in the past. In developed countries, smoking accounts for approximately 66% of new cases of bladder cancer in men and 30% of cases in women.
Currently, avoidance of cigarette smoking is the most effective public-health measure against bladder cancer. At least half of current cases of bladder cancers could be prevented by smoking cessation among current smokers.1
Passive smoking may also increase risk of bladder cancer. In a recent European study, exposure to environmental tobacco smoke (ETS) during childhood (but not adulthood) increased the risk of bladder cancer by 40%.2 Another study showed a three-fold increased risk of bladder cancer in women heavily exposed to ETS in childhood, although no association for men. This study showed an even higher five-fold risk increase for women most heavily exposed to ETS throughout their lifetime.3 A study of bladder cancer incidence in the offspring of men and women diagnosed with lung cancer found a significant increase in risk of bladder cancer in those whose mothers had lung cancer, but no increased risk for paternal lung cancer. The authors interpret this as evidence that exposure to tobacco carcinogens in utero or while breastfeeding may lead to bladder cancer in later life.4
References:
Scélo G, Brennan P. The epidemiology of bladder and kidney cancer. Nat Clin Pract Urol. 2007; 4(4):205–17.
Bjerregaard BK, Raaschou-Nielsen O, Sørensen M, Frederiksen K, Christensen J, Tiønneland A, et al. Tobacco smoke and bladder cancer—in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2006; 119(10):2412–6.
Jiang X, Yuan JM, Skipper PL, Tannenbaum SR, Yu MC, Environmental tobacco smoke and bladder cancer risk in never smokers of Los Angeles County. Cancer Res. 2007; 67(15):7540–5.
Hemminki K, Chen B. Parental lung cancer as predictor of cancer risks in offspring: clues about multiple routes of harmful influence? Int J Cancer. 2006; 118(3):744–8.
1. Scélo and Brennan 2007; 2. Bjerregaard et al. 2006; 3. Jiang et al. 2007

7. Tobacco and Kidney Cancer
Cigarette smoking has consistently been observed to be a risk factor for kidney, renal pelvis, and ureter cancer.
Smokers are at an approximately 50% increased risk of developing this cancer compared with never smokers.
Notes:
A number of studies have also demonstrated a dose–response relationship with increased tobacco use, with relative risks of developing kidney cancer for heavy smokers ranging from twofold to threefold compared with those who have never smoked. This risk seems to decline over time after smoking cessation. Population-attributable risk estimates indicate that cigarette smoking, both past and present, is responsible for approximately 20% of kidney cancer cases among men, and for 10% of cases among women. Approximately half of this population-attributable risk is due to current smoking. Currently, the main avoidable causes of kidney cancer are cigarette smoking, excess body weight, and hypertension, which together are likely to account for up to 60% of all cases of these tumors.1
The epidemiology of cancers of the renal pelvis or ureter is similar to that of transitional-cell bladder cancer. The main risk factor is cigarette smoking, with increased risks for smokers of black tobacco. Reductions in risk after quitting smoking have been seen in almost all studies.1
Reference:
Scélo G, Brennan P. The epidemiology of bladder and kidney cancer. Nat Clin Pract Urol. 2007; 4(4):205–17. Available at
Scélo and Brennan 2007

8. Cessation and Bladder Cancer
Tobacco has a late-stage effect in carcinogenesis, and the decrease in risk continues with time since smoking cessation.1
Smoking cessation reduces risk, but risk in ex-smokers remains higher than never-smokers for more than 20 years.2
Notes:
Bladder and kidney cancer together account for about 5% of cancers worldwide, and represent the 9th and 14th most common cancers in terms of absolute numbers, respectively. A number of important occupational, lifestyle, and genetic factors have been implicated in bladder carcinogenesis. An immediate decrease in risk of bladder cancer (of around 40%) is observed among both men and women who stop smoking, which implies that tobacco has a late-stage effect in carcinogenesis, and the decrease in risk continues with time since smoking cessation. Much of the risk associated with smoking is likely to result from aromatic amines present in cigarette smoke, including benzidine, 4-aminobiphenyl, naphthylamine and 4-chloro- ortho-toluidine.
This decrease of bladder cancer was over 30% after 1–4 years of smoking cessation, OR = 0.65 (95% CI = 0. 53–0.79), and was over 60% after 25 years of cessation, OR = 0.37 (95% CI = 0. 30–0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers.2
References:
Scélo G, Brennan P. The epidemiology of bladder and kidney cancer. Nat Clin Pract Urol. 2007; 4(4):205–17. Available at
Brennan P, Bogillot O, Cordier S, Greiser E, Schill W, Vineis P, et al. Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies. Int J Cancer. 2000; 86(2):
1. Scélo and Brennan 2007; 2. Brennan et al. 2000

9. OPTIONAL SLIDES Tobacco and Urogenital Cancer Mini Lecture 4
Module: Tobacco Effects and Neoplasia

10. Tobacco and Urogenital Cancers: Mechanism
Benzidine, 4-aminobiphenyl, naphthylamine, and 4-chloro-ortho- toluidine in cigarette smoke lead to risk of bladder carcinoma.1
Smokers have decreased natural killer cell activity and impaired T lymphocyte suppressor cell function compared with nonsmokers.2
One in vitro study found reduced natural killer cell activity of peripheral blood mononuclear cells in patients with advanced prostate cancer compared with controls.3
Notes:
Bladder and kidney cancer together account for about 5% of cancers worldwide, and represent the 9th and 14th most common cancers in terms of absolute numbers, respectively.
References:
Scélo G, Brennan P. The epidemiology of bladder and kidney cancer. Nat Clin Pract Urol. 2007; 4(4):205–17. Available at
Hughes DA, Haslam PL, Townsend PJ, Turner-Warwick M. Numerical and functional alterations in circulatory lymphocytes in cigarette smokers. Clin Exp Immunol. 1985; 61:459–66.
Lahat N, Alexander B, Levin D, Moskovitz B. The relationship between clinical stage, natural killer activity and related immunological parameters in adenocarcinoma of the prostate. Cancer Immunol Immunother. 1989; 28:208–12.
1. Scélo and Brennan 2007; 2. Hughes et al.1985; 3. Lahat et al.1989

11. The most important health message a doctor can give to patients is to quit smoking.