Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder

Siamak Daneshmand, MD
Section Editor
Derek Raghavan, MD, PhD, FACP, FASCO
Deputy Editor
Michael E Ross, MD


Bladder cancer is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide [1]. Urothelial (previously known as transitional cell) carcinoma is the predominant histologic type in the United States and Western Europe, where it accounts for approximately 90 percent of bladder cancers. In other areas of the world, such as the Middle East, non-urothelial histologies are more frequent, due at least in part to the prevalence of schistosomiasis.

Studies of urothelial bladder cancer have identified multiple risk factors, the most important of which are cigarette smoking and various occupational exposures. Numerous other factors have also been identified that may play an etiologic role in some cases of urothelial cancer, although interpretation of the evidence is frequently confounded by exposure to tobacco use.

The epidemiology and risk factors associated with urothelial cancer of the bladder will be reviewed here. Non-urothelial bladder cancer is discussed separately. (See "Non-urothelial bladder cancer".)


Incidence and prevalence — Bladder cancer is the ninth most common cancer in the world, with 430,000 new cases diagnosed in 2012 [2]. In the United States, approximately 79,000 new cases and 17,000 deaths occur each year due to bladder cancer [3]. In Europe, there were an estimated 118,000 cases and 52,000 deaths in 2012 [4]. In developed regions such as North America and Europe, bladder cancer is predominantly urothelial.

From 1985 to 2005, the number of bladder cancers diagnosed in the United States increased by over 50 percent, while from 1975 to 1996 the five-year survival rate for those diagnosed with bladder cancer increased from 75 to 81 percent [5,6]. Mortality rates in several western European countries have shown similar downward trends over the last two decades, but are still increasing in some eastern European countries [7].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: May 2017. | This topic last updated: May 31, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol 2009; 27:289.
  2. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65:87.
  3. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  4. Marcos-Gragera R, Mallone S, Kiemeney LA, et al. Urinary tract cancer survival in Europe 1999-2007: Results of the population-based study EUROCARE-5. Eur J Cancer 2015.
  5. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55:10.
  6. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277.
  7. Pelucchi C, Bosetti C, Negri E, et al. Mechanisms of disease: The epidemiology of bladder cancer. Nat Clin Pract Urol 2006; 3:327.
  8. Feldman AR, Kessler L, Myers MH, Naughton MD. The prevalence of cancer. Estimates based on the Connecticut Tumor Registry. N Engl J Med 1986; 315:1394.
  9. Vercelli M, Quaglia A, Parodi S, Crosignani P. Cancer prevalence in the elderly. ITAPREVAL Working Group. Tumori 1999; 85:391.
  10. Michaud DS, Clinton SK, Rimm EB, et al. Risk of bladder cancer by geographic region in a U.S. cohort of male health professionals. Epidemiology 2001; 12:719.
  11. Lynch CF, Cohen MB. Urinary system. Cancer 1995; 75:316.
  12. Scosyrev E, Noyes K, Feng C, Messing E. Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer 2009; 115:68.
  13. Hinotsu S, Akaza H, Miki T, et al. Bladder cancer develops 6 years earlier in current smokers: analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association. Int J Urol 2009; 16:64.
  14. Freedman ND, Abnet CC, Caporaso NE, et al. Impact of changing US cigarette smoking patterns on incident cancer: risks of 20 smoking-related cancers among the women and men of the NIH-AARP cohort. Int J Epidemiol 2016; 45:846.
  15. Linn JF, Sesterhenn I, Mostofi FK, Schoenberg M. The molecular characteristics of bladder cancer in young patients. J Urol 1998; 159:1493.
  16. Ryerson AB, Eheman CR, Altekruse SF, et al. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer 2016; 122:1312.
  17. Schulz MR, Loomis D. Occupational bladder cancer mortality among racial and ethnic minorities in 21 states. Am J Ind Med 2000; 38:90.
  18. Rabbani F, Perrotti M, Russo P, Herr HW. Upper-tract tumors after an initial diagnosis of bladder cancer: argument for long-term surveillance. J Clin Oncol 2001; 19:94.
  19. Kang CH, Yu TJ, Hsieh HH, et al. The development of bladder tumors and contralateral upper urinary tract tumors after primary transitional cell carcinoma of the upper urinary tract. Cancer 2003; 98:1620.
  20. Jones TD, Wang M, Eble JN, et al. Molecular evidence supporting field effect in urothelial carcinogenesis. Clin Cancer Res 2005; 11:6512.
  21. Hartmann A, Schlake G, Zaak D, et al. Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res 2002; 62:809.
  22. Hafner C, Knuechel R, Stoehr R, Hartmann A. Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies. Int J Cancer 2002; 101:1.
  23. Sidransky D, Frost P, Von Eschenbach A, et al. Clonal origin of bladder cancer. N Engl J Med 1992; 326:737.
  24. Louhelainen J, Wijkström H, Hemminki K. Allelic losses demonstrate monoclonality of multifocal bladder tumors. Int J Cancer 2000; 87:522.
  25. Kogevinas M, 't Mannetje A, Cordier S, et al. Occupation and bladder cancer among men in Western Europe. Cancer Causes Control 2003; 14:907.
  26. Vineis P, Pirastu R. Aromatic amines and cancer. Cancer Causes Control 1997; 8:346.
  27. Steineck G, Plato N, Norell SE, Hogstedt C. Urothelial cancer and some industry-related chemicals: an evaluation of the epidemiologic literature. Am J Ind Med 1990; 17:371.
  28. Freedman ND, Silverman DT, Hollenbeck AR, et al. Association between smoking and risk of bladder cancer among men and women. JAMA 2011; 306:737.
  29. Cumberbatch MG, Rota M, Catto JW, La Vecchia C. The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. Eur Urol 2016; 70:458.
  30. Hoffman D, Masuda Y, Wynder EL. Alpha-naphthylamine and beta-naphthylamine in cigarette smoke. Nature 1969; 221:255.
  31. Hecht SS. Cigarette smoking: cancer risks, carcinogens, and mechanisms. Langenbecks Arch Surg 2006; 391:603.
  32. Brennan P, Bogillot O, Cordier S, et al. Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies. Int J Cancer 2000; 86:289.
  33. Brennan P, Bogillot O, Greiser E, et al. The contribution of cigarette smoking to bladder cancer in women (pooled European data). Cancer Causes Control 2001; 12:411.
  34. Pietzak EJ, Mucksavage P, Guzzo TJ, Malkowicz SB. Heavy Cigarette Smoking and Aggressive Bladder Cancer at Initial Presentation. Urology 2015; 86:968.
  35. Chen CH, Shun CT, Huang KH, et al. Stopping smoking might reduce tumour recurrence in nonmuscle-invasive bladder cancer. BJU Int 2007; 100:281.
  36. Skipper PL, Tannenbaum SR, Ross RK, Yu MC. Nonsmoking-related arylamine exposure and bladder cancer risk. Cancer Epidemiol Biomarkers Prev 2003; 12:503.
  37. Jiang X, Yuan JM, Skipper PL, et al. Environmental tobacco smoke and bladder cancer risk in never smokers of Los Angeles County. Cancer Res 2007; 67:7540.
  38. Jung I, Messing E. Molecular mechanisms and pathways in bladder cancer development and progression. Cancer Control 2000; 7:325.
  39. Cole P, Hoover R, Friedell GH. Occupation and cancer of the lower urinary tract. Cancer 1972; 29:1250.
  40. CASE RA, HOSKER ME, McDONALD DB, PEARSON JT. Tumours of the urinary bladder in workmen engaged in the manufacture and use of certain dyestuff intermediates in the British chemical industry. I. The role of aniline, benzidine, alpha-naphthylamine, and beta-naphthylamine. Br J Ind Med 1954; 11:75.
  41. Pira E, Piolatto G, Negri E, et al. Bladder cancer mortality of workers exposed to aromatic amines: a 58-year follow-up. J Natl Cancer Inst 2010; 102:1096.
  42. Gaertner RR, Trpeski L, Johnson KC, Canadian Cancer Registries Epidemiology Research Group. A case-control study of occupational risk factors for bladder cancer in Canada. Cancer Causes Control 2004; 15:1007.
  43. Smailyte G, Kurtinaitis J, Andersen A. Mortality and cancer incidence among Lithuanian cement producing workers. Occup Environ Med 2004; 61:529.
  44. Zeegers MP, Swaen GM, Kant I, et al. Occupational risk factors for male bladder cancer: results from a population based case cohort study in the Netherlands. Occup Environ Med 2001; 58:590.
  45. Boffetta P, Dosemeci M, Gridley G, et al. Occupational exposure to diesel engine emissions and risk of cancer in Swedish men and women. Cancer Causes Control 2001; 12:365.
  46. Ma F, Fleming LE, Lee DJ, et al. Mortality in Florida professional firefighters, 1972 to 1999. Am J Ind Med 2005; 47:509.
  47. Youakim S. Risk of cancer among firefighters: a quantitative review of selected malignancies. Arch Environ Occup Health 2006; 61:223.
  48. LeMasters GK, Genaidy AM, Succop P, et al. Cancer risk among firefighters: a review and meta-analysis of 32 studies. J Occup Environ Med 2006; 48:1189.
  49. Haas NS, Gochfeld M, Robson MG, Wartenberg D. Latent health effects in firefighters. Int J Occup Environ Health 2003; 9:95.
  50. Ames BN, Kammen HO, Yamasaki E. Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc Natl Acad Sci U S A 1975; 72:2423.
  51. Henley SJ, Thun MJ. Use of permanent hair dyes and bladder-cancer risk. Int J Cancer 2001; 94:903.
  52. Hartge P, Hoover R, Altman R, et al. Use of hair dyes and risk of bladder cancer. Cancer Res 1982; 42:4784.
  53. Czene K, Tiikkaja S, Hemminki K. Cancer risks in hairdressers: assessment of carcinogenicity of hair dyes and gels. Int J Cancer 2003; 105:108.
  54. La Vecchia C, Tavani A. Hair dyes and bladder cancer: an update. Eur J Cancer Prev 2001; 10:205.
  55. Gago-Dominguez M, Castelao JE, Yuan JM, et al. Use of permanent hair dyes and bladder-cancer risk. Int J Cancer 2001; 91:575.
  56. Villanueva CM, Fernández F, Malats N, et al. Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer. J Epidemiol Community Health 2003; 57:166.
  57. Chevrier C, Junod B, Cordier S. Does ozonation of drinking water reduce the risk of bladder cancer? Epidemiology 2004; 15:605.
  58. Marshall G, Ferreccio C, Yuan Y, et al. Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J Natl Cancer Inst 2007; 99:920.
  59. Tsai SM, Wang TN, Ko YC. Cancer mortality trends in a blackfoot disease endemic community of Taiwan following water source replacement. J Toxicol Environ Health A 1998; 55:389.
  60. Chen CJ, Chuang YC, You SL, et al. A retrospective study on malignant neoplasms of bladder, lung and liver in blackfoot disease endemic area in Taiwan. Br J Cancer 1986; 53:399.
  61. Moore LE, Smith AH, Eng C, et al. Arsenic-related chromosomal alterations in bladder cancer. J Natl Cancer Inst 2002; 94:1688.
  62. Chen CH, Chiou HY, Hsueh YM, et al. Clinicopathological characteristics and survival outcome of arsenic related bladder cancer in taiwan. J Urol 2009; 181:547.
  63. Michaud DS, Spiegelman D, Clinton SK, et al. Fluid intake and the risk of bladder cancer in men. N Engl J Med 1999; 340:1390.
  64. Silverman DT, Alguacil J, Rothman N, et al. Does increased urination frequency protect against bladder cancer? Int J Cancer 2008; 123:1644.
  65. Lai MN, Wang SM, Chen PC, et al. Population-based case-control study of Chinese herbal products containing aristolochic acid and urinary tract cancer risk. J Natl Cancer Inst 2010; 102:179.
  66. Bejany DE, Lockhart JL, Rhamy RK. Malignant vesical tumors following spinal cord injury. J Urol 1987; 138:1390.
  67. Delnay KM, Stonehill WH, Goldman H, et al. Bladder histological changes associated with chronic indwelling urinary catheter. J Urol 1999; 161:1106.
  68. Groah SL, Weitzenkamp DA, Lammertse DP, et al. Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer. Arch Phys Med Rehabil 2002; 83:346.
  69. Michaud DS, Platz EA, Giovannucci E. Gonorrhoea and male bladder cancer in a prospective study. Br J Cancer 2007; 96:169.
  70. Matanoski GM, Elliott EA. Bladder cancer epidemiology. Epidemiol Rev 1981; 3:203.
  71. Magee PN, Barnes JM. Carcinogenic nitroso compounds. Adv Cancer Res 1967; 10:163.
  72. Schoppmann SF, Birner P, Stöckl J, et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol 2002; 161:947.
  73. Nathan C. Points of control in inflammation. Nature 2002; 420:846.
  74. Leibovici D, Grossman HB, Dinney CP, et al. Polymorphisms in inflammation genes and bladder cancer: from initiation to recurrence, progression, and survival. J Clin Oncol 2005; 23:5746.
  75. Li N, Yang L, Zhang Y, et al. Human papillomavirus infection and bladder cancer risk: a meta-analysis. J Infect Dis 2011; 204:217.
  76. Raman JD, Sosa RE, Vaughan ED Jr, Scherr DS. Pathologic features of bladder tumors after nephroureterectomy or segmental ureterectomy for upper urinary tract transitional cell carcinoma. Urology 2007; 69:251.
  77. Matsui Y, Utsunomiya N, Ichioka K, et al. Risk factors for subsequent development of bladder cancer after primary transitional cell carcinoma of the upper urinary tract. Urology 2005; 65:279.
  78. Castellan M, Gosalbez R, Perez-Brayfield M, et al. Tumor in bladder reservoir after gastrocystoplasty. J Urol 2007; 178:1771.
  79. Soergel TM, Cain MP, Misseri R, et al. Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropathic bladder. J Urol 2004; 172:1649.
  80. Shaw J, Lewis MA. Bladder augmentation surgery--what about the malignant risk? Eur J Pediatr Surg 1999; 9 Suppl 1:39.
  81. Baydar DE, Allan RW, Castellan M, et al. Anaplastic signet ring cell carcinoma arising in gastrocystoplasty. Urology 2005; 65:1226.
  82. Kleinerman RA, Boice JD Jr, Storm HH, et al. Second primary cancer after treatment for cervical cancer. An international cancer registries study. Cancer 1995; 76:442.
  83. Travis LB, Curtis RE, Storm H, et al. Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst 1997; 89:1429.
  84. Sandhu JS, Vickers AJ, Bochner B, et al. Clinical characteristics of bladder cancer in patients previously treated with radiation for prostate cancer. BJU Int 2006; 98:59.
  85. Bostrom PJ, Soloway MS, Manoharan M, et al. Bladder cancer after radiotherapy for prostate cancer: detailed analysis of pathological features and outcome after radical cystectomy. J Urol 2008; 179:91.
  86. Shah SK, Lui PD, Baldwin DD, Ruckle HC. Urothelial carcinoma after external beam radiation therapy for prostate cancer. J Urol 2006; 175:2063.
  87. Yee DS, Shariat SF, Lowrance WT, et al. Impact of previous radiotherapy for prostate cancer on clinical outcomes of patients with bladder cancer. J Urol 2010; 183:1751.
  88. Keehn A, Ludmir E, Taylor J, Rabbani F. Incidence of bladder cancer after radiation for prostate cancer as a function of time and radiation modality. World J Urol 2017; 35:713.
  89. Travis LB, Curtis RE, Glimelius B, et al. Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J Natl Cancer Inst 1995; 87:524.
  90. Talar-Williams C, Hijazi YM, Walther MM, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996; 124:477.
  91. O'Keane JC. Carcinoma of the urinary bladder after treatment with cyclophosphamide. N Engl J Med 1988; 319:871.
  92. Pedersen-Bjergaard J, Ersbøll J, Hansen VL, et al. Carcinoma of the urinary bladder after treatment with cyclophosphamide for non-Hodgkin's lymphoma. N Engl J Med 1988; 318:1028.
  93. Habs MR, Schmähl D. Prevention of urinary bladder tumors in cyclophosphamide-treated rats by additional medication with the uroprotectors sodium 2-mercaptoethane sulfonate (mesna) and disodium 2,2'-dithio-bis-ethane sulfonate (dimesna). Cancer 1983; 51:606.
  94. Piper JM, Tonascia J, Matanoski GM. Heavy phenacetin use and bladder cancer in women aged 20 to 49 years. N Engl J Med 1985; 313:292.
  95. Porpáczy P, Schramek P. Analgesic nephropathy and phenacetin-induced transitional cell carcinoma - analysis of 300 patients with long-term consumption of phenacetin-containing drugs. Eur Urol 1981; 7:349.
  96. Fortuny J, Kogevinas M, Zens MS, et al. Analgesic and anti-inflammatory drug use and risk of bladder cancer: a population based case control study. BMC Urol 2007; 7:13.
  97. Blumentals WA, Foulis PR, Schwartz SW, Mason TJ. Analgesic therapy and the prevention of bladder cancer. Urol Oncol 2004; 22:11.
  98. Genkinger JM, De Vivo I, Stampfer MJ, et al. Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow-up study. Int J Cancer 2007; 120:2221.
  99. Castaño-Vinyals G, Cantor KP, Malats N, et al. Air pollution and risk of urinary bladder cancer in a case-control study in Spain. Occup Environ Med 2008; 65:56.
  100. Soll-Johanning H, Bach E. Occupational exposure to air pollution and cancer risk among Danish urban mail carriers. Int Arch Occup Environ Health 2004; 77:351.
  101. Sontag JM. Experimental identification of genitourinary carcinogens. Urol Clin North Am 1980; 7:803.
  102. Armstrong BK. Saccharin/cyclamates: epidemiological evidence. IARC Sci Publ 1985; :129.
  103. Morrison AS. Advances in the etiology of urothelial cancer. Urol Clin North Am 1984; 11:557.
  104. Zeegers MP, Tan FE, Goldbohm RA, van den Brandt PA. Are coffee and tea consumption associated with urinary tract cancer risk? A systematic review and meta-analysis. Int J Epidemiol 2001; 30:353.
  105. Sala M, Cordier S, Chang-Claude J, et al. Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case-control studies in European countries. Cancer Causes Control 2000; 11:925.
  106. Zeegers MP, Dorant E, Goldbohm RA, van den Brandt PA. Are coffee, tea, and total fluid consumption associated with bladder cancer risk? Results from the Netherlands Cohort Study. Cancer Causes Control 2001; 12:231.
  107. Takkouche B, Etminan M, Montes-Martínez A. Personal use of hair dyes and risk of cancer: a meta-analysis. JAMA 2005; 293:2516.
  108. Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994; 86:1600.
  109. Plna K, Hemminki K. Familial bladder cancer in the National Swedish Family Cancer Database. J Urol 2001; 166:2129.
  110. Aben KK, Witjes JA, Schoenberg MP, et al. Familial aggregation of urothelial cell carcinoma. Int J Cancer 2002; 98:274.
  111. Lin J, Spitz MR, Dinney CP, et al. Bladder cancer risk as modified by family history and smoking. Cancer 2006; 107:705.
  112. Murta-Nascimento C, Silverman DT, Kogevinas M, et al. Risk of bladder cancer associated with family history of cancer: do low-penetrance polymorphisms account for the increase in risk? Cancer Epidemiol Biomarkers Prev 2007; 16:1595.
  113. Shariat SF, Tokunaga H, Zhou J, et al. p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer. J Clin Oncol 2004; 22:1014.
  114. Sidransky D, Von Eschenbach A, Tsai YC, et al. Identification of p53 gene mutations in bladder cancers and urine samples. Science 1991; 252:706.
  115. Malats N, Bustos A, Nascimento CM, et al. P53 as a prognostic marker for bladder cancer: a meta-analysis and review. Lancet Oncol 2005; 6:678.
  116. Cote RJ, Dunn MD, Chatterjee SJ, et al. Elevated and absent pRb expression is associated with bladder cancer progression and has cooperative effects with p53. Cancer Res 1998; 58:1090.
  117. Cordon-Cardo C, Wartinger D, Petrylak D, et al. Altered expression of the retinoblastoma gene product: prognostic indicator in bladder cancer. J Natl Cancer Inst 1992; 84:1251.
  118. Grossman HB, Liebert M, Antelo M, et al. p53 and RB expression predict progression in T1 bladder cancer. Clin Cancer Res 1998; 4:829.
  119. Lipponen PK, Liukkonen TJ. Reduced expression of retinoblastoma (Rb) gene protein is related to cell proliferation and prognosis in transitional-cell bladder cancer. J Cancer Res Clin Oncol 1995; 121:44.
  120. Quentin T, Henke C, Korabiowska M, et al. Altered mRNA expression of the Rb and p16 tumor suppressor genes and of CDK4 in transitional cell carcinomas of the urinary bladder associated with tumor progression. Anticancer Res 2004; 24:1011.
  121. Li L, Yang T, Lian X. Effects of exogenous wild-type P16 gene transfection on the expression of cell cycle-related proteins in bladder cancer cell line. Cancer Invest 2005; 23:309.
  122. Benedict WF, Lerner SP, Zhou J, et al. Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer. Oncogene 1999; 18:1197.
  123. Friedrich MG, Blind C, Milde-Langosch K, et al. Frequent p16/MTS1 inactivation in early stages of urothelial carcinoma of the bladder is not associated with tumor recurrence. Eur Urol 2001; 40:518.
  124. Kader AK, Shao L, Dinney CP, et al. Matrix metalloproteinase polymorphisms and bladder cancer risk. Cancer Res 2006; 66:11644.
  125. Lin J, Spitz MR, Wang Y, et al. Polymorphisms of folate metabolic genes and susceptibility to bladder cancer: a case-control study. Carcinogenesis 2004; 25:1639.
  126. Papathoma AS, Petraki C, Grigorakis A, et al. Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer. Anticancer Res 2000; 20:2009.
  127. Mommsen S, Aagaard J, Sell A. An epidemiological case-control study of bladder cancer in males from a predominantly rural district. Eur J Cancer Clin Oncol 1982; 18:1205.
  128. Branch RA, Chern HD, Adedoyin A, et al. The procarcinogen hypothesis for bladder cancer: activities of individual drug metabolizing enzymes as risk factors. Pharmacogenetics 1995; 5 Spec No:S97.
  129. Butler MA, Iwasaki M, Guengerich FP, Kadlubar FF. Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci U S A 1989; 86:7696.
  130. Kaisary A, Smith P, Jaczq E, et al. Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors. Cancer Res 1987; 47:5488.
  131. Bryant MS, Vineis P, Skipper PL, Tannenbaum SR. Hemoglobin adducts of aromatic amines: associations with smoking status and type of tobacco. Proc Natl Acad Sci U S A 1988; 85:9788.
  132. Kaderlik KR, Kadlubar FF. Metabolic polymorphisms and carcinogen-DNA adduct formation in human populations. Pharmacogenetics 1995; 5 Spec No:S108.
  133. Hein DW. N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk. Oncogene 2006; 25:1649.
  134. Okkels H, Sigsgaard T, Wolf H, Autrup H. Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking. Cancer Epidemiol Biomarkers Prev 1997; 6:225.
  135. Bell DA, Taylor JA, Paulson DF, et al. Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 1993; 85:1159.
  136. Yu MC, Ross RK, Chan KK, et al. Glutathione S-transferase M1 genotype affects aminobiphenyl-hemoglobin adduct levels in white, black and Asian smokers and nonsmokers. Cancer Epidemiol Biomarkers Prev 1995; 4:861.
  137. García-Closas M, Malats N, Silverman D, et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 2005; 366:649.
  138. Dong LM, Potter JD, White E, et al. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 2008; 299:2423.