Urinary Bladder Cancer Risk Factors: A Lebanese Case-Control Study

  • Published : 2013.05.30


Background: Bladder cancer is the second most incident malignancy among Lebanese men. The purpose of this study was to investigate potential risk factors associated with this observed high incidence. Methods: A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently selected from the same settings. Data were collected using interview questionnaire and blood analysis. Exposure data were collected using a structured face-to-face interview questionnaire. Blood samples were collected to determine N-acetyltransferase1 (NAT1) genotype by PCR-RFLP. Analyses revolved around univariate, bivariate and multivariate logistic regression, along with checks for effect modification. Results: The odds of having bladder cancer among smokers was 1.02 times significantly higher in cases vs. controls. The odds of exposure to occupational diesel or fuel combustion fumes were 4.1 times significantly higher in cases vs controls. The odds of prostate-related morbidity were 5.6 times significantly higher in cases vs controls. Cases and controls showed different clustering patterns of NAT1 alleles. No significant differences between cases and controls were found for consumption of alcohol, coffee, tea, or artificial sweeteners. Conclusions: This is the first case-control study investigating bladder cancer risk factors in the Lebanese context. Results confirmed established risk factors in the literature, particularly smoking and occupational exposure to diesel. The herein observed associations should be used to develop appropriate prevention policies and intervention strategies, in order to control this alarming disease in Lebanon.


  1. Axtell C, Ward E, McCabe G, et al (1998). Underlying and multiple cause mortality in a cohort of workers exposed to aromatic amines. Am J Ind Med, 34, 506-11<506::AID-AJIM12>3.0.CO;2-5
  2. Band P, Le N, MacArthur A, et al (2005). Identification of occupational cancer risks in British Columbia: a populationbased case-control study of 1129 cases of bladder cancer. J Occup Environ Med, 47, 854-8
  3. Brennan P, Bogillot O, Cordier S, et al (2000). Cigarette smoking and bladder cancer in men: a pooled analysis of 11casecontrol studies. Int J Cancer, 86, 289-94<289::AID-IJC21>3.0.CO;2-M
  4. Butcher N, Ilett K, Minchin R (1998). Functional polymorphism of the human arylamine N-acetyltransferase type 1 gene caused by C190T and G560A mutations. Pharmacogenetics, 8, 67-72
  5. Clavel J, Mandereau L, Limasset J, et al (1994). Occupational exposure to polycyclic aromatic hydrocarbons and the risk of bladder cancer. Int J Epidemiol, 23, 1145-53
  6. Deitz A, Doll M, Hein D (1997). A restriction fragment length polymorphism assay that differentiates human N-acetyltransferase-1 (NAT1). Anal Biochem, 253, 219-24
  7. Dhaini H, Levy G (2000). Arylamine N-acetyltransferase 1 (NAT1) genotypes in a Lebanese population. Pharmacogenetics, 10, 79-83
  8. Ferlay J, Shin H, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917
  9. Gago-Dominguez M, Bell D, Watson M, et al (2003). Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2. Carcinogenesis, 24, 483-9
  10. Hein D, Doll M, Fretland A, et al (2000). Molecular genetics and epidemiology of the NAT1 and NAT2 Acetylation Polymorphism. Cancer Epidemiol Biomarkers Prev, 9, 29-42
  11. Hein D, Grant D, Sim E (2000). Update on consensus arylamine N-acetyltransferase gene nomenclature. Pharmacogenetics, 10, 291-2
  12. Hoover R, Strasser P (1980). Artificial sweeteners and human bladder cancer: preliminary results. Lancet, 1, 837-40
  13. Hughes N, Janezic S, McQueen K, et al (1998). Identification and characterization of variant alleles of human acetyltranferase NAT1 with defective function using p-aminosalicylate as an in-vivo and in-vitro probe. Pharmacogenetics, 8, 55-66
  14. Iyer V, E. Harris R, Wynder E (1990). Diesel exhaust exposure and bladder cancer risk. Eur J Epidemiol, 6, 49-54
  15. Jankovic S, Radosavljevic V (2007). Risk factors for bladder cancer. Tumori, 93, 4-12
  16. Jemal R, Bray F, Center M, et al (2011). Global Cancer Statistics. CA Cancer J Clin, 61, 69-90
  17. Kellen E, Zeegers M, Paulussen A, et al (2007). Does occupational exposure to PAHs, diesel and aromatic amines interact with smoking and metabolic genetic polymorphisms to increase the risk on bladder cancer?; The Belgian case control study on bladder cancer risk. Cancer Lett, 245, 51-60
  18. Kogevinas M, Mannetje A, Cordier S, et al (2003). Occupation and bladder cancer among men in Western Europe. Cancer Causes Control, 14, 907-14
  19. Kogevinas M, Trichopoulos D (2002). Urinary bladder cancer. In: Adami H, Hunter D, Trichopoulos D (eds). Textbook of cancer epidemiology. New York: Oxford University Press, 1, 446-66.
  20. La Vecchia C, Negri E (1996). Nutrition and bladder cancer. Cancer Causes Control, 7, 95-100
  21. MOPH, Lebanese Ministry of Public Health-Epidemiological Surveillance Program (2010). National Cancer Registry 2007 Cancer Data.
  22. Mostafa M, Sheweita S, O'Connor P (1999). Relationship between Schistosomiasis and Bladder Cancer. Clin Microbiol Rev, 12, 97-111
  23. Nakkash R, Khalil J, Afifi R (2011). The rise in narghile (shisha, hookah) waterpipe tobacco smoking: a qualitative study of perceptions of smokers and non smokers. Biomed Central Public Hlth, 14, 315
  24. Negri E, La Vecchia C (2001). Epidemiology and prevention of bladder cancer. Eur J Cancer Prev, 10, 7-14
  25. Olfert S, Felknor S, Delclos G (2006). An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures. South Med J, 99, 1256-63
  26. Pashos C, Botteman M, Laskin B, et al (2002). Bladder cancer: epidemiology, diagnosis, and management. Cancer Pract, 10, 311-22
  27. Ploeg M, Aben K, Kiemeney L (2009). The present and future burden of urinary bladder cancer in the world. World J Urol, 27, 289-93
  28. Renwick A (1993). A data-derived safety (uncertainty) factor for the intense sweetener, saccharin. Food Addit Contam, 10, 337-50
  29. Saade G, Abou Jaoude S, Afifi R, et al (2008). Patterns of tobacco use: results from the 2005 Global Youth Tobacco Survey in Lebanon. East Mediterr Hlth J, 16, 1280-9
  30. Samanic C, Kogevinas M, Dosemeci M, et al (2006). Smoking and bladder cancer in Spain: effects of tobacco type, timing, environmental tobacco smoke, and gender. Cancer Epidemiol Biomarkers Prev, 15, 1348-54
  31. Schoenberg J, Stemhagen A, Mogielnicki A, et al (1984). Casecontrol study of bladder cancer in New Jersey I. J Natl Cancer Inst, 72, 973-81
  32. Shamseddine A, Musallam K (2010). Cancer Epidemiology in Lebanon. Middle East J Cancer, 1, 41-4
  33. Shamseddine A, Sibai A, Gehchan N, et al (2004). Cancer incidence in postwar Lebanon: findings from the first national population-based registry, 1998. Ann Epidemiol, 14, 663-8
  34. Vineis P, Marinelli D, Autrup H, et al (2001). Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: a pooled analysis of genotype-based studies. Cancer Epidemiol Biomarkers Prev, 10, 1249-52
  35. Wakai K, Hirose K, Takezaki T, et al (2004). Foods and beverages in relation to urothelial cancer: case-control study in Japan. Int J Urol, 11, 11-9
  36. Wilhelm-Benartzi C, Christensen B, Koestler D, et al (2011). Association of secondhand smoke exposures with DNA methylation in bladder carcinomas. Cancer Causes Control, 22, 1205-13
  37. World Health Organization. Combating the tobacco epidemic. Geneva: WHO, 1999.
  38. Yamaguchi N, Tazaki H, Okubo T, et al (1982). Periodic urine cytology surveillance of bladder tumor incidence in dyestuff workers. Am J Ind Med, 3, 139-48
  39. Yassine IA, Kobeissi L, Jabbour ME, et al (2012). N-Acetyltransferase 1 (NAT1) Genotype: a risk factor for urinary bladder cancer in a Lebanese population. J Oncol, 2012, 512976
  40. Zeegers M, Kellen E, Buntinx F, et al (2004). The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review. World J Urol, 21, 392-401
  41. Zeegers M, Swaen G, Kant I, et al (2001). Occupational risk factors for male bladder cancer: results from a population based case cohort study in the Netherlands. Occup Environ Med, 58, 590-6
  42. Zheng Y, Amr S, Saleh D, et al (2012). Urinary Bladder Cancer Risk Factors in Egypt: A Multicenter Case-Control Study. Cancer Epidemiol Biomarkers Prev, 21, 537-46

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