Effects of change in smoking habits on bladder cancer incidence in Tunisia


Bladder cancer is among the most frequently diagnosed cancer. Tobacco smoking exposures involving nitrosamines and aromatic amines are the main cause of bladder cancer. Although cigarette consumption has gradually decreased, an increased incidence of bladder cancer was registered among males Tunisian for the last two decades. A similar increased incidence of lung adenocarcinoma and bladder cancer was registered among Tunisian males. Epidemiological results suggest that changes in cigarette smoking may be the cause of the increased incidence of bladder cancer. The relationship between CYP1A2 enzyme activities, a key enzyme for activation of bladder carcinogens, and bladder cancer risk was investigated. Variations in CYP1 A2 activities measured in patients with bladder cancer and healthy smokers showed a signifycantly higher CYP1A2 metabolic activity in patient group. Changing in cigarette smoking habits associated to the variation in CYP1A2 activity seem to explain partly the increase incidence of bladder cancer observed in Tunisian male population.

Share and Cite:

Mrizak, D. , B'chir, F. , Jaidane, M. , Arnaud, M. and Saguem, S. (2011) Effects of change in smoking habits on bladder cancer incidence in Tunisia. Health, 3, 613-619. doi: 10.4236/health.2011.310103.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Parkin, D.M., Pisani, P. and Ferlay, J. (1994) At least one of seven cases of cancer is caused by smoking. Global estimate for 1985. International Journal of Cancer, 59, 494-504. doi:10.1002/ijc.2910590411
[2] Pelluchi, C., Bosetti, C., Negri, E., Malvezzi, M. and La Vecchia, C. (2006) Mechanisms of disease: The epidemiology of bladder cancer. Nature Clinical Practice Urology, 3, 327-340. doi:10.1038/ncpuro0510
[3] Baris, D. et al. (2009) A case-control study of smoking and bladder cancer risk: Emergent patterns over time. Journal of the National Cancer Institute, 101, 1553-1561. doi:10.1093/jnci/djp361
[4] Boffetta, P. (2008) Tobacco smoking and risk of bladder cancer. Scandinavian Journal of Urology and Nephrology, 42, 45-54. doi:10.1080/03008880802283664
[5] Samanic, C., Kogevinas, M., Dosemeci, M., Malats, N., Real, F.X., Garcia-Closas, M., Serra, C., Carrato, A., Garc?′a-Closas, R., Sala, M., Lloreta, J., Tardon, A., Rothman, N. and Silverman, D.T. (2006) Smoking and Bladder Cancer in Spain: Effects of Tobacco Type, Timing, Environmental Tobacco Smoke, and Gender. Cancer Epdemio Markers, 15, 1345-1354.
[6] Van Hemelrijck M. J. J., Michaud, D.S., Connolly, G.N. and Kabir, Z. (2009) Tobacco use and bladder cancer patterns in three western European countries. Journal of Public Health, 31, 335-344. doi:10.1093/pubmed/fdp062
[7] Raman, J.D., Messer, J., Sielatycki, J.A. and Hollenbeak, C.S. (2010) Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, British Journal of Urology International, 107, 1059-1064.
[8] Alberg, A.J. and Hebert, J.R. (2009) Cigarette Smoking and Bladder Cancer: A New Twist in an Old Saga? Journal of the National Cancer Institute, 101, 1525-1526. doi:10.1093/jnci/djp385
[9] López, A.G., González, C.A., Errezola, M., Escolar, A., Izarzugaza, I., Nebot, M. and Riboli, E. (1991) Tobacco smoke inhalation pattern, tobacco type, and bladder cancer in Spain. American Journal of Epidemiology, 134, 830-839.
[10] Hoffmann, D., Rivenson, A., Chung, F.L. and Wynder, E.L. (1993) Potential inhibitors of tobacco carcinogenesis. Annals of the New York Academy of Sciences, 28, 140-160. doi:10.1111/j.1749-6632.1993.tb39169.x
[11] Arnaud, M.J. (1993) Metabolism of caffeine and other components of coffee. In: Garattini, S. Ed., Caffeine, Coffee and Health, Raven Press, New York.
[12] B’chir, F., Laouani, A., Ksibi, S., Arnaud, M.J. and Saguem, S. (2007) Cigarette filter and the incidence of lung adenocarcinoma among Tunisian population. Lung cancer Amsterdam Netherlands, 57, 26-33. doi:10.1016/j.lungcan.2007.01.034
[13] Lilienfeld, A.M., Levin, M. and Moore, G.E. (1956) The association of smoking with cancer of the urinary bladder in humans. Archives of Internal Medicine, 98, 129-135.
[14] U. S. Department of Health and Human Services. (2004) The Health Consequences of Smoking, A Report of the Surgeon General, Atlanta.
[15] Gandini, S. et al. (2008) Tobacco smoking and cancer: A meta-analysis. International Journal of Cancer, 122, 5-64. doi:10.1002/ijc.23033
[16] Gough, K.R., Read, A.E., McCarthy, C.F. and Waters, A.H. (1963) Megaloblastic anaemia due to nutritional deficiency of folic acid. QJM, 32, 243-256.
[17] Chanarin, I., MacGibbon, B.M., O’Sullivan, W.J. and Mollin, D.L. (1959) Folic-acid deficiency in pregnancy. The pathogenesis of megaloblastic anaemia of pregnancy. Lancet, 2, 634-639. doi:10.1016/S0140-6736(59)91409-6
[18] Pavanello, S., Mastrangelo, G., Placidi, D., Campagna, M., Pulliero, A., Carta, A., Arici, A. and Porru, S. (2010) CYP1A2 polymorphisms, occupational and environmental exposures and risk of bladder cancer. European Journal of Epidemiology, 25, 491-500. doi:10.1007/s10654-010-9479-8
[19] Van der Boon J. (2001) Low-tar ?lter cigarettes and an aggressive type of lung cancer. Lancet Oncology, 2, 255. doi:10.1016/S1470-2045(00)00310-7
[20] Hoffmann, D., Rivenson, A., Murphy, S.E., Chung, F.L., Amin, S. and Hecht, S.S. (1993) Cigarette smoking and adenocarcinoma of the lung: The relevance of nicotine- derived N-nitrosamines. Journal of Smoking Related Disorder, 4, 165-189.
[21] Wogan, G.N., Hecht, S.S., Felton, J.S., Conney, A.H. and Loeb, L.A. (2004) Environmental and chemical carcinogenesis. Seminars in Cancer Biology, 14, 473-486. doi:10.1016/j.semcancer.2004.06.010
[22] Morabia, A. and Wynder, E.L. (1991) Cigarette smoking and lung cancer cell types. Cancer, 68, 2074-2048. doi:10.1002/1097-0142(19911101)68:9<2074::AID-CNCR2820680939>3.0.CO;2-X
[23] Wald, N., Idle, M. and Smith, P.G. (1977) Carboxyhaemoglobin levels in smokers of filter and plain cigarettes. The Lancet, 1, 110-112. doi:10.1016/S0140-6736(77)91702-0
[24] Lubin, J.H., Alavanja, M.C.R., Caporaso, N., Brown, L.M., Brownson, R.C., Field, R.W., Garcia-Closas, M., Hartge, P., Hauptmann, M., Hayes, R.B., Kleinerman, R., Kogevinas M, Krewski D, Langholz B, Le tourneau E G, Lynch. C.F, Malats, N., Sandler, N.P., Schaffrath-Rosario, A., Schoenberg, J.B., Silverman, D.T., Wang, Z., Wichmann, H.E., Wilcox, H.B. and Zielinski, J.M. (2007) Cigarette smoking and cancer risk: Modeling total exposure and intensity. American Journal of Epidemiology, 166, 479-489.
[25] Hoffmann, D., Brunnemann, K.D., Prokopczyk, B. and Djordjevic, M.V. (1994) Tobacco-specific N-nitrosamines and Areca-derived N-nitrosamines: Chemistry, biochemistry, carcinogenicity and relevance to humans. Journal of Toxicology and Environmental Health, 41, 1-52. doi:10.1080/15287399409531825
[26] Hecht, S.S., Isaacs, S. and Trushin, N. (1994) Lung tumor induction in A/J mice by the tobacco smoke carcingens4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone and benzo (a) pyrene: A potentially useful model for evaluation of chemopreventive agents. Carcinogenesis, 15, 2721-2725. doi:10.1093/carcin/15.12.2721
[27] Balansky, R., Ganchev, G., ltcheva, M., Steele, V.E., D’ Agostini1, F. and De Flora S. (2007) Potent carcinogenicity of cigarette smoke in mice exposed early in life. Carcinogenesis, 28, 2236-2243. doi:10.1093/carcin/bgm122
[28] Landi, M.T., Sinha, R., Lang, N.P. and Kadlubar, F.F. (1999) Human cytochrome P4501A2. In: Vineis, P., Malats, N., Lang, M., d’Errico, A., Caporaso, N., Cuzick, J. and Moffetta, P., Eds., Metabolic polymorphisms and susceptibility to cancer. IARC Scientific Publications, Lyon, 173-195.
[29] Vineis, P., Talaska, G., Malaveille, C., Bartsch, H., Martone, T., Sithisarankul, P. and Strickland, P. (1996) DNA adducts in urothelial cells: Relationship with biomarkers of exposure to arylamines and polycyclic aromatic hydrocarbons from tobacco smoke. International Journal of Cancer, 65, 314-316. doi:10.1002/(SICI)1097-0215(19960126)65:3<314::AID-IJC6>3.0.CO;2-2
[30] Bonser, G.M., Bradshaw, L., Clayson, D.B. and Jull, J.W. (1956) A further study of the carcinogenic properties of ortho hydroxy-amines and related compounds by bladder implantation in the mouse. British Journal of Cancer, 10, 539-546. doi:10.1038/bjc.1956.63
[31] Lee, S.W., Jang, I.J., Shin, S.G., Lee, K.H., Yim, D.S., Kim, S.W., Oh, S.J. and Lee, S.H. (1994) CYP1A2 activity as a risk factor for bladder cancer. Journal of Korean Medical Science, 9, 482-489.
[32] Guengerich, F.P. and Shimada, T. (1991) Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chemical Research in Toxicology, 4, 391-407. doi:10.1021/tx00022a001
[33] Kamataki, T., Fujita, K., Nakayama, K., Yamazaki, Y., Miyamoto, M. and Ariyoshi, N. (2002) Role of human cytochrome P450 (CYP) in the metabolic activation of nitrosamine derivatives: Application of genetically engineered Salmonella expressing human CYP. Drug Metabolism Reviews, 34, 667-676. doi:10.1081/DMR-120005668
[34] Landi, M.T., Zocchetti, C., Bernucci, M., Kadlubar, F.F., Tannenbaum, S., Skipper, P., Bartsch, H., Malaveille, C., shields, P., Caporaso, N. and Vinei, P. (1996) CytochromeP4501A2: Enzyme Induction and Genetic Control, Determining 4-aminobiphenyl-hemoglobin Adduct Levels. Cancer Epidemiology, Biomarkers & Prevention, 5, 693-698.
[35] Le Marchand, L., Hankin, J.H., Wilkens, L.R., Pierce, L.M., Franke, A., Kolonel, L.N., Seifried, A., Custer, L.J., Chang, W., Lum, J.A. and Donlon, T. (2001) Combined Effects of Well-done Red Meat, Smoking, and Rapid N-Acetyltransferase 2 and CYP1A2 Phenotypes in Increasing Colorectal Cancer Risk. Cancer Epidemiology, Biomarkers & Prevention, 10, 1259-1266.
[36] Working group on the Evaluation of Carcinogenic Risks to Humans. (2004) Tobacco smoke and involuntary smoking. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Lyon, 1-1438.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.