Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers
Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers
Chamssuddin, Abdou K.; Saadat, Seyed H.; Deiri, Kusay; Zarzar, Mohamed Y.; Abdouche, Naji; Deeb, Omar; Alia, Loauy
2013-06-01 00:00:00
Arab Journal of Urology (2013) 11, 165–168 Arab Journal of Urology (Official Journal of the Arab Association of Urology) www.sciencedirect.com ONCOLOGY/RECONSTRUCTION ORIGINAL ARTICLE Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers Abdou K. Chamssuddin , Seyed H. Saadat, Kusay Deiri, Mohamed Y. Zarzar, Naji Abdouche, Omar Deeb, Loauy Alia Section Urology, Surgical Department, AlBairouni University Hospital, College of Medicine, Damascus, Syria Received 31 October 2012, Received in revised form 24 December 2012, Accepted 26 December 2012 Available online 8 February 2013 KEYWORDS Abstract Objectives: To evaluate the role of smoking as a risk factor for higher stages and grades of bladder cancer, for although smoking is considered to be one Female; of the most important risk factors for bladder cancer, its relationship to grade Male; and stage is not clear. Risk Factors; Patients and methods: In all, 300 patients diagnosed with bladder cancer were Smoking; studied to compare the grade and stage and bladder cancer between non-smokers, Urinary bladder low-dose, moderate-dose and high-dose smokers. neoplasms Results: The smokers and non-smokers had no significant difference in tumour grade or stage (P = 0.702 for grade and 0.166 for stage) but the high-dose group had significantly higher grades and stages than the other groups (P = 0.026, odds ratio 4.8, 95% confidence interval 1.2–19.1 for grade, and 0.037, 10.91 and 1.16– 102.6, respectively, for stage). Conclusion: Smoking has a potential dose-dependent effect on the grade and stage of bladder cancer, with high-dose smokers having more aggressive disease. The equality in the aggressiveness of the cancer between smokers in general and non- smokers might be a result of the hazardous effect of passive smoking in countries where smoking is a common habit. ª 2013 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. Corresponding author. Tel.: +963 944 717684/11 2321431. E-mail address: drchamssuddin@gmail.com (A.K. Chamssuddin). Introduction Peer review under responsibility of Arab Association of Urology. TCC of the bladder is one of the most common urolog- ical malignancies worldwide. Bladder cancer is an Production and hosting by Elsevier increasingly common disease, and is estimated to be- 2090-598X ª 2013 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.aju.2012.12.009 166 Chamssuddin et al. come more prevalent as the population ages. There is a smoker group, only 21 patients (8.7%) were low-dose strong association between cigarette smoking and blad- smokers, with 202 (84.1%) moderate-dose and 17 der cancer. While specific industrial chemicals have been (7.1%) high-dose smokers. linked to the development of this disease, 60% of blad- The smokers and non-smokers had no significant dif- der cancers are estimated to result from smoking [1]. ference in mean age and tumour grade or stage Therefore cigarette smoking is the most important risk (P = 0.702 for grade and 0.166 for stage; Table 1). factor for the development of TCC of the urinary blad- Comparing the high-, moderate- and low-dose smok- der [2]. ers, the high-dose group had significantly higher grades Experimental evidence suggests that nitrosamines, and stages than the other groups (Table 1). The differ- 2-naphthylamine and 4-aminobiphenyl might be the ence between moderate- and low-dose smokers was bladder carcinogens in cigarette smoke [3]. These amines not significant for grade or stage (Table 1). cause oxidative DNA damage in the normal urothelium and induce bladder cancer [4]. Discussion The association between bladder cancer and smoking has been studied and evaluated from different aspects, Tobacco smoking is the main known cause of TCC in especially in relation to gender [5–7], intensity and dura- humans. In most populations, over half of cases in tion of smoking [8,9], ceasing smoking [8], environmen- men and an important proportion in women are attrib- tal tobacco smoking [6,9], and cigarettes vs. other types utable to this habit. Epidemiological studies conducted of smoking [6,10]. in different populations have shown a linear relationship It is not clear whether smoking contributes to the between the intensity and duration of smoking and the development of higher grades and stages of bladder can- risk of developing a bladder cancer [6]. cer. Studies assessing this issue are few and have given The management of bladder cancer is governed by conflicting results. In the present study we tried to eval- specific guidelines, and the stage and grade of cancer uate the role of smoking, as a separate risk factor, in are the most important factors influencing these guide- higher stages and grades of bladder cancer. lines. As the grade and stage of bladder cancer are the most important prognostic factors, any link between Patients and methods other variables (e.g. gender, tumour volume and tumour multiplicity) and these two factors should also be We reviewed the records of the last 300 patients in our addressed. hospital who had undergone transurethral resection of The link between smoking and grade or stage, as a a bladder tumour and were diagnosed with bladder can- sole risk factor, has not been examined in sufficient de- cer. We documented their cigarette smoking habit, and tail. Mohseni et al. [11] found that smoking was not only patients were categorised into two groups accordingly, the most important risk factor for TCC of the urinary i.e. smokers (defined as smoking of P10 cigarettes/day bladder, but was also associated with higher grades of for the last 3 years), and non-smokers, who had no pre- the tumour. Also, Marsit et al. [12] reported that smok- vious history of cigarette smoking. The first group was ing not only induced bladder cancer, but also, once subdivided arbitrarily into three groups, i.e. low-, developed, it could increase the grade of the tumour, moderate- and high- dose smokers, defined as smoking 10–29, 30–59 and P60 cigarettes/day, respectively. We then compared the stage and grade of cancer among Table A comparison of smokers and non-smokers, and intensity of smoking, for tumour grade and stage. G1 tumours these groups. Grade 1 tumours were considered as are considered low-grade, and PG2 as high-grade. Ta and T1 low-grade and if grade P2 as high-grade; for stage, tu- tumours are considered low-stage, and PT2 as high-stage. mours of 6T1 were considered as low-stage and PT2 as Group (n) Grade, n (%) Stage, n (%) high-stage tumours. The statistical analysis included descriptive statistics High Low High Low and logistic regression to calculate the odds ratio and Smokers (240) 70 (29) 170 (71) 65 (19) 175 (81) 95% CI, with P < 0.05 considered to indicate Non-smokers (60) 16 (26) 44 (74) 11 (17) 49 (83) P 0.702 0.166 significance. Odds ratio 1.132 1.655 95% CI 0.599–2.14 0.811–3.38 Results Dose High (17) 12 (71) 5 (29) 6 (35) 11 (65) The mean (range) age of the patients was 47 (30–80) Moderate (202) 51 (25) 151 (75) 12 (6) 190 (94) years; 285 were men (95%) and 15 were women (5%). Low (21) 7 (33) 14 (67) 1 (5) 20 (95) P 0.026 0.037 Of the 300 patients, 240 (80%) were smokers and 60 Odds ratio 4.8 10.91 (20%) were non-smokers. The female to male ratio in 95% CI 1.2–19.1 1.16–102.6 the smoker group was 1:39 (6/234 patients). In the Evaluation of grade and stage in patients with bladder cancer 167 resulting in a worse prognosis. In these two studies the In conclusion, smoking has a potential dose-depen- relationship of smoking with tumour stage was not dis- dent effect on the grade and stage of bladder cancer, cussed. Thompson et al. [13] reviewed the records of 386 with high-dose smokers having more aggressive disease. patients diagnosed with TCC of the bladder, to deter- The equality in the aggressiveness of the cancer between mine any correlation between smoking history and the low- to moderate-dose smokers and the non-smokers stage, grade and number of recurrences of TCC. There in the present population might be a result of the effect was a significant association between the smoking his- of passive smoking, in a country where smoking is a tory and all three variables. common habit, or it might be the result of other risk fac- Fleshner et al. [14] conducted a retrospective cohort tors. To answer these questions, a population-based study to assess the influence of tobacco exposure, at study is needed, with more patients and studying all the time of diagnosis, on the disease-related outcomes environmental factors, including smoking. of superficial TCC. They tried to define the relationship of various smoking habits with the disease recurrence Conflict of interest rate and TCC-related adverse events. They found that there were no significant differences among ex-smokers, None of the authors have conflicts of interest that are those who had smoked, and continuing smokers in terms relevant to this study. of stage, grade, tumour size, multifocality, immediate BCG therapy, or the median duration of the follow-up. Funding Using data from 1860 patients with bladder cancer and 3934 population-based controls from the National No financial grants or other funding were relevant to Bladder Cancer Study, Sturgeon et al. [15] examined this study. None of the authors had any industrial links the relationship between suspected bladder cancer risk or affiliations. factors and tumour stage and grade. They found that cigarette smoking increased the risk of both non- References muscle-invasive and muscle-invasive bladder tumours, but the effect of smoking was more obvious in the higher [1] Silverman DT, Devesa SS, Moore LL, Rothman N. Bladder cancer. In: Schottenfeld D, Fraumeni Jr JF, editors. Cancer stages (heavy smokers had a relative risk of 3.0 for non- epidemiology and prevention. New York, NY: Oxford University muscle-invasive disease but had a relative risk of 5.2 for Press; 2006. p. 1101–27. muscle-invasive tumours). This association was not seen [2] Golka K, Schmidt T, Seidel T, Dietrich H, Roemer HC, Lohlein with grade. D, et al. The influence of polymorphisms of glutathione S- The present study was conducted in the authors’ transferases M1 and M3 on the development of human urothelial cancer. J Toxicol Environ Health A 2008;71:881–6. oncological hospital, which is the only one in the Syria [3] Riedel K, Scherer G, Engl J, Hagedorn HW, Tricker AR. specialising in the management of malignancies. The Determination of three carcinogenic aromatic amines in urine of large number of patients with bladder cancer (300) were smokers and nonsmokers. J Anal Toxicol 2006;30:187–95. from all regions in Syria, with no racial or ethnic dis- [4] Arizono K, Osada Y, Kuroda Y. DNA repair gene hOGG1 crimination. There was no significant difference between codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population. Jpn J Clin Oncol smokers and non-smokers in grade or stage, but the 2008;38:186–91. high-dose smokers had significantly more aggressive [5] Hemelt M, Yamamoto H, Cheng KK, Zeegers MP. The effect of cancer (P < 0.05). smoking on the male excess of bladder cancer: a meta-analysis Although it remains to be determined whether the and geographical analyses. Int J Cancer 2009;124:412–9. non-smokers had other risk factors that might contrib- [6] Boffetta P. Tobacco smoking and risk of bladder cancer. Scand J Urol Nephrol Suppl 2008;218:45–54. ute to the induction of high-grade and high-stage blad- [7] Zeegers MP, Goldbohm RA, van den Brandt PA. A prospective der cancer, the insignificant difference between the study on active and environmental tobacco smoking and bladder groups could also be explained by the fact that smoking cancer risk. Cancer Causes Control 2002;13:83–90 [The is a very common habit in Syria and thus even non- Netherlands]. smokers are commonly exposed to cigarette smoke. [8] Samanic C, Kogevinas M, Dosemeci M, Malats N, Real FX, Garcia-Closas M, et al. Smoking and bladder cancer in Spain: Our conclusion that high-dose smokers had a more effects of tobacco type, timing, environmental tobacco smoke, aggressive cancer not only supports this explanation, and gender. Cancer Epidemiol Biomarkers Prev 2006;15:1348–54. but also again shows the dose-dependent relationship [9] Alberg AJ, Kouzis A, Genkinger JM, Gallicchio L, Burke AE, between smoking and bladder cancer, although there Hoffman SC, et al. A prospective cohort study of bladder cancer were only 17 heavy smokers of the 240 smokers, which risk in relation to active cigarette smoking and household exposure to secondhand cigarette smoke. Am J Epidemiol restricted the value of the statistical analyses. 2007;165:660–6. Thus from our results we strongly advise heavy smok- [10] Pitard A, Brennan P, Clavel J, Greiser E, Lopez-Abente G, ers to stop smoking, or at least to smoke fewer cigarettes Chang-Claude J, et al. Cigar, pipe, and cigarette smoking and per day, as we found that a greater dose of smoking was bladder cancer risk in European men. Cancer Causes Control associated with the higher grades of bladder cancer. 2001;12:551–6. 168 Chamssuddin et al. [11] Mohseni M, Nourbakhsh A, Hatami Z-N. Association of [14] Fleshner N, Garland J, Moadel A, Herr H, Ostroff J, Trambert smoking with high-grade transitional cell carcinoma of the R, et al. Influence of smoking status on the disease-related urinary bladder. Arch Iranian Med 2005;8:286–9. outcomes of patients with tobacco-associated superficial transi- [12] Marsit CJ, Houseman EA, Schned AR, Karagas MR, Kelsey KT. tional cell carcinoma of the bladder. Cancer 1999;86:2337–45. Promoter hypermethylation is associated with current smoking, [15] Sturgeon SR, Hartge P, Silverman DT, Kantor AF, Linehan age, gender and survival in bladder cancer. Carcinogenesis C, Lynch C, et al. Associations between bladder cancer risk 2007;28:1745–51. factors and tumor stage and grade at diagnosis. Epidemiology [13] Thompson IM, Peek M, Rodriguez FR. The impact of cigarette 1994;5:218–25. smoking on stage, grade, and number of recurrences of transi- tional cell carcinoma of the bladder. J Urol 1987;137:401–3.
http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.pngArab Journal of UrologyTaylor & Francishttp://www.deepdyve.com/lp/taylor-francis/evaluation-of-grade-and-stage-in-patients-with-bladder-cancer-among-CVfn2WAnOA
Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers
Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers
Abstract
AbstractObjectives:To evaluate the role of smoking as a risk factor for higher stages and grades of bladder cancer, for although smoking is considered to be one of the most important risk factors for bladder cancer, its relationship to grade and stage is not clear.Patients and methods:In all, 300 patients diagnosed with bladder cancer were studied to compare the grade and stage and bladder cancer between non-smokers, low-dose, moderate-dose and high-dose smokers.Results:The smokers and...
Arab Journal of Urology (2013) 11, 165–168 Arab Journal of Urology (Official Journal of the Arab Association of Urology) www.sciencedirect.com ONCOLOGY/RECONSTRUCTION ORIGINAL ARTICLE Evaluation of grade and stage in patients with bladder cancer among smokers and non-smokers Abdou K. Chamssuddin , Seyed H. Saadat, Kusay Deiri, Mohamed Y. Zarzar, Naji Abdouche, Omar Deeb, Loauy Alia Section Urology, Surgical Department, AlBairouni University Hospital, College of Medicine, Damascus, Syria Received 31 October 2012, Received in revised form 24 December 2012, Accepted 26 December 2012 Available online 8 February 2013 KEYWORDS Abstract Objectives: To evaluate the role of smoking as a risk factor for higher stages and grades of bladder cancer, for although smoking is considered to be one Female; of the most important risk factors for bladder cancer, its relationship to grade Male; and stage is not clear. Risk Factors; Patients and methods: In all, 300 patients diagnosed with bladder cancer were Smoking; studied to compare the grade and stage and bladder cancer between non-smokers, Urinary bladder low-dose, moderate-dose and high-dose smokers. neoplasms Results: The smokers and non-smokers had no significant difference in tumour grade or stage (P = 0.702 for grade and 0.166 for stage) but the high-dose group had significantly higher grades and stages than the other groups (P = 0.026, odds ratio 4.8, 95% confidence interval 1.2–19.1 for grade, and 0.037, 10.91 and 1.16– 102.6, respectively, for stage). Conclusion: Smoking has a potential dose-dependent effect on the grade and stage of bladder cancer, with high-dose smokers having more aggressive disease. The equality in the aggressiveness of the cancer between smokers in general and non- smokers might be a result of the hazardous effect of passive smoking in countries where smoking is a common habit. ª 2013 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. Corresponding author. Tel.: +963 944 717684/11 2321431. E-mail address: drchamssuddin@gmail.com (A.K. Chamssuddin). Introduction Peer review under responsibility of Arab Association of Urology. TCC of the bladder is one of the most common urolog- ical malignancies worldwide. Bladder cancer is an Production and hosting by Elsevier increasingly common disease, and is estimated to be- 2090-598X ª 2013 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.aju.2012.12.009 166 Chamssuddin et al. come more prevalent as the population ages. There is a smoker group, only 21 patients (8.7%) were low-dose strong association between cigarette smoking and blad- smokers, with 202 (84.1%) moderate-dose and 17 der cancer. While specific industrial chemicals have been (7.1%) high-dose smokers. linked to the development of this disease, 60% of blad- The smokers and non-smokers had no significant dif- der cancers are estimated to result from smoking [1]. ference in mean age and tumour grade or stage Therefore cigarette smoking is the most important risk (P = 0.702 for grade and 0.166 for stage; Table 1). factor for the development of TCC of the urinary blad- Comparing the high-, moderate- and low-dose smok- der [2]. ers, the high-dose group had significantly higher grades Experimental evidence suggests that nitrosamines, and stages than the other groups (Table 1). The differ- 2-naphthylamine and 4-aminobiphenyl might be the ence between moderate- and low-dose smokers was bladder carcinogens in cigarette smoke [3]. These amines not significant for grade or stage (Table 1). cause oxidative DNA damage in the normal urothelium and induce bladder cancer [4]. Discussion The association between bladder cancer and smoking has been studied and evaluated from different aspects, Tobacco smoking is the main known cause of TCC in especially in relation to gender [5–7], intensity and dura- humans. In most populations, over half of cases in tion of smoking [8,9], ceasing smoking [8], environmen- men and an important proportion in women are attrib- tal tobacco smoking [6,9], and cigarettes vs. other types utable to this habit. Epidemiological studies conducted of smoking [6,10]. in different populations have shown a linear relationship It is not clear whether smoking contributes to the between the intensity and duration of smoking and the development of higher grades and stages of bladder can- risk of developing a bladder cancer [6]. cer. Studies assessing this issue are few and have given The management of bladder cancer is governed by conflicting results. In the present study we tried to eval- specific guidelines, and the stage and grade of cancer uate the role of smoking, as a separate risk factor, in are the most important factors influencing these guide- higher stages and grades of bladder cancer. lines. As the grade and stage of bladder cancer are the most important prognostic factors, any link between Patients and methods other variables (e.g. gender, tumour volume and tumour multiplicity) and these two factors should also be We reviewed the records of the last 300 patients in our addressed. hospital who had undergone transurethral resection of The link between smoking and grade or stage, as a a bladder tumour and were diagnosed with bladder can- sole risk factor, has not been examined in sufficient de- cer. We documented their cigarette smoking habit, and tail. Mohseni et al. [11] found that smoking was not only patients were categorised into two groups accordingly, the most important risk factor for TCC of the urinary i.e. smokers (defined as smoking of P10 cigarettes/day bladder, but was also associated with higher grades of for the last 3 years), and non-smokers, who had no pre- the tumour. Also, Marsit et al. [12] reported that smok- vious history of cigarette smoking. The first group was ing not only induced bladder cancer, but also, once subdivided arbitrarily into three groups, i.e. low-, developed, it could increase the grade of the tumour, moderate- and high- dose smokers, defined as smoking 10–29, 30–59 and P60 cigarettes/day, respectively. We then compared the stage and grade of cancer among Table A comparison of smokers and non-smokers, and intensity of smoking, for tumour grade and stage. G1 tumours these groups. Grade 1 tumours were considered as are considered low-grade, and PG2 as high-grade. Ta and T1 low-grade and if grade P2 as high-grade; for stage, tu- tumours are considered low-stage, and PT2 as high-stage. mours of 6T1 were considered as low-stage and PT2 as Group (n) Grade, n (%) Stage, n (%) high-stage tumours. The statistical analysis included descriptive statistics High Low High Low and logistic regression to calculate the odds ratio and Smokers (240) 70 (29) 170 (71) 65 (19) 175 (81) 95% CI, with P < 0.05 considered to indicate Non-smokers (60) 16 (26) 44 (74) 11 (17) 49 (83) P 0.702 0.166 significance. Odds ratio 1.132 1.655 95% CI 0.599–2.14 0.811–3.38 Results Dose High (17) 12 (71) 5 (29) 6 (35) 11 (65) The mean (range) age of the patients was 47 (30–80) Moderate (202) 51 (25) 151 (75) 12 (6) 190 (94) years; 285 were men (95%) and 15 were women (5%). Low (21) 7 (33) 14 (67) 1 (5) 20 (95) P 0.026 0.037 Of the 300 patients, 240 (80%) were smokers and 60 Odds ratio 4.8 10.91 (20%) were non-smokers. The female to male ratio in 95% CI 1.2–19.1 1.16–102.6 the smoker group was 1:39 (6/234 patients). In the Evaluation of grade and stage in patients with bladder cancer 167 resulting in a worse prognosis. In these two studies the In conclusion, smoking has a potential dose-depen- relationship of smoking with tumour stage was not dis- dent effect on the grade and stage of bladder cancer, cussed. Thompson et al. [13] reviewed the records of 386 with high-dose smokers having more aggressive disease. patients diagnosed with TCC of the bladder, to deter- The equality in the aggressiveness of the cancer between mine any correlation between smoking history and the low- to moderate-dose smokers and the non-smokers stage, grade and number of recurrences of TCC. There in the present population might be a result of the effect was a significant association between the smoking his- of passive smoking, in a country where smoking is a tory and all three variables. common habit, or it might be the result of other risk fac- Fleshner et al. [14] conducted a retrospective cohort tors. To answer these questions, a population-based study to assess the influence of tobacco exposure, at study is needed, with more patients and studying all the time of diagnosis, on the disease-related outcomes environmental factors, including smoking. of superficial TCC. They tried to define the relationship of various smoking habits with the disease recurrence Conflict of interest rate and TCC-related adverse events. They found that there were no significant differences among ex-smokers, None of the authors have conflicts of interest that are those who had smoked, and continuing smokers in terms relevant to this study. of stage, grade, tumour size, multifocality, immediate BCG therapy, or the median duration of the follow-up. Funding Using data from 1860 patients with bladder cancer and 3934 population-based controls from the National No financial grants or other funding were relevant to Bladder Cancer Study, Sturgeon et al. [15] examined this study. None of the authors had any industrial links the relationship between suspected bladder cancer risk or affiliations. factors and tumour stage and grade. They found that cigarette smoking increased the risk of both non- References muscle-invasive and muscle-invasive bladder tumours, but the effect of smoking was more obvious in the higher [1] Silverman DT, Devesa SS, Moore LL, Rothman N. Bladder cancer. In: Schottenfeld D, Fraumeni Jr JF, editors. Cancer stages (heavy smokers had a relative risk of 3.0 for non- epidemiology and prevention. New York, NY: Oxford University muscle-invasive disease but had a relative risk of 5.2 for Press; 2006. p. 1101–27. muscle-invasive tumours). This association was not seen [2] Golka K, Schmidt T, Seidel T, Dietrich H, Roemer HC, Lohlein with grade. D, et al. The influence of polymorphisms of glutathione S- The present study was conducted in the authors’ transferases M1 and M3 on the development of human urothelial cancer. J Toxicol Environ Health A 2008;71:881–6. oncological hospital, which is the only one in the Syria [3] Riedel K, Scherer G, Engl J, Hagedorn HW, Tricker AR. specialising in the management of malignancies. The Determination of three carcinogenic aromatic amines in urine of large number of patients with bladder cancer (300) were smokers and nonsmokers. J Anal Toxicol 2006;30:187–95. from all regions in Syria, with no racial or ethnic dis- [4] Arizono K, Osada Y, Kuroda Y. DNA repair gene hOGG1 crimination. There was no significant difference between codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population. Jpn J Clin Oncol smokers and non-smokers in grade or stage, but the 2008;38:186–91. high-dose smokers had significantly more aggressive [5] Hemelt M, Yamamoto H, Cheng KK, Zeegers MP. The effect of cancer (P < 0.05). smoking on the male excess of bladder cancer: a meta-analysis Although it remains to be determined whether the and geographical analyses. Int J Cancer 2009;124:412–9. non-smokers had other risk factors that might contrib- [6] Boffetta P. Tobacco smoking and risk of bladder cancer. Scand J Urol Nephrol Suppl 2008;218:45–54. ute to the induction of high-grade and high-stage blad- [7] Zeegers MP, Goldbohm RA, van den Brandt PA. A prospective der cancer, the insignificant difference between the study on active and environmental tobacco smoking and bladder groups could also be explained by the fact that smoking cancer risk. Cancer Causes Control 2002;13:83–90 [The is a very common habit in Syria and thus even non- Netherlands]. smokers are commonly exposed to cigarette smoke. [8] Samanic C, Kogevinas M, Dosemeci M, Malats N, Real FX, Garcia-Closas M, et al. Smoking and bladder cancer in Spain: Our conclusion that high-dose smokers had a more effects of tobacco type, timing, environmental tobacco smoke, aggressive cancer not only supports this explanation, and gender. Cancer Epidemiol Biomarkers Prev 2006;15:1348–54. but also again shows the dose-dependent relationship [9] Alberg AJ, Kouzis A, Genkinger JM, Gallicchio L, Burke AE, between smoking and bladder cancer, although there Hoffman SC, et al. A prospective cohort study of bladder cancer were only 17 heavy smokers of the 240 smokers, which risk in relation to active cigarette smoking and household exposure to secondhand cigarette smoke. Am J Epidemiol restricted the value of the statistical analyses. 2007;165:660–6. Thus from our results we strongly advise heavy smok- [10] Pitard A, Brennan P, Clavel J, Greiser E, Lopez-Abente G, ers to stop smoking, or at least to smoke fewer cigarettes Chang-Claude J, et al. Cigar, pipe, and cigarette smoking and per day, as we found that a greater dose of smoking was bladder cancer risk in European men. Cancer Causes Control associated with the higher grades of bladder cancer. 2001;12:551–6. 168 Chamssuddin et al. [11] Mohseni M, Nourbakhsh A, Hatami Z-N. Association of [14] Fleshner N, Garland J, Moadel A, Herr H, Ostroff J, Trambert smoking with high-grade transitional cell carcinoma of the R, et al. Influence of smoking status on the disease-related urinary bladder. Arch Iranian Med 2005;8:286–9. outcomes of patients with tobacco-associated superficial transi- [12] Marsit CJ, Houseman EA, Schned AR, Karagas MR, Kelsey KT. tional cell carcinoma of the bladder. Cancer 1999;86:2337–45. Promoter hypermethylation is associated with current smoking, [15] Sturgeon SR, Hartge P, Silverman DT, Kantor AF, Linehan age, gender and survival in bladder cancer. Carcinogenesis C, Lynch C, et al. Associations between bladder cancer risk 2007;28:1745–51. factors and tumor stage and grade at diagnosis. Epidemiology [13] Thompson IM, Peek M, Rodriguez FR. The impact of cigarette 1994;5:218–25. smoking on stage, grade, and number of recurrences of transi- tional cell carcinoma of the bladder. J Urol 1987;137:401–3.
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