Bladder cancer

The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF).

Cancer

H-ras (activating mutation) [HSA:3265] [KO:K02833]
FGFR3 (activating mutation) [HSA:2261] [KO:K05094]
p16/INK4A (homozygous deletion or hypermethylation) [HSA:1029] [KO:K06621]
p53 (inactivating mutation or deletion) [HSA:7157] [KO:K04451]
RB1 (deletion or hyperphosphorylation) [HSA:5925] [KO:K06618]
EGFR (overexpression) [HSA:1956] [KO:K04361]
ERBB2 (overexpression) [HSA:2064] [KO:K05083]
RASSF1 (hypermethylation) [HSA:11186] [KO:K09850]
DAPK1 (hypermethylation) [HSA:1612] [KO:K08803]

Aluminium production
4-Aminobiphenyl [CPD:C10998]
Arsenic in drinking-water
Auramine, manufacture of
Benzidine [CPD:C16444]
Benzo[a]pyrene [CPD:C07535]
N,N-Bis(2-chloroethyl)-2-naphthylamine (Chlornaphazine)
Coal gasification
Coal-tar pitches [CPD:C16451]
Coal-tars [DR:D03573]
Herbal remedies containing plant species of the genus Aristolochia
Magenta, manufacture of
2-Naphthylamine [CPD:C02227]
Paving and roofing with coal-tar pitch
Radium-224 and its decay products [CPD:C16455]
Schistosoma haematobium (infection with)
Shale-oils [CPD:C16458]
Tobacco smoking and tobacco smoke
X- and gamma-radiation

Thiotepa [DR:D00583]
Valrubicin [DR:D02697]
Cisplatin [DR:D00275]
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574]
Durvalumab [DR:D10808]
Avelumab [DR:D10817]
Atezolizumab [DR:D10773]

ICD-O: 8120/3, Tumor type: Infiltrating urothelial carcinoma
ICD-O: 8120/2, Tumor type: Urothelial carcinoma in situ
ICD-O: 8130/23, Tumor type: Non-invasive papillary urothelial carcinoma, high grade
ICD-O: 8130/21, Tumor type: Non-invasive papillary urothelial carcinoma, low grade

PMID:16110317 (tumor type)

Wu XR.

Urothelial tumorigenesis: a tale of divergent pathways.

Nat Rev Cancer 5:713-25 (2005)
DOI:10.1038/nrc1697

PMID:17149381

Sugano K, Kakizoe T.

Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.

Nat Clin Pract Urol 3:642-52 (2006)
DOI:10.1038/ncpuro0649

PMID:16474624

Wolff EM, Liang G, Jones PA.

Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.

Nat Clin Pract Urol 2:502-10 (2005)
DOI:10.1038/ncpuro0318

PMID:17158541

Mitra AP, Datar RH, Cote RJ.

Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification.

J Clin Oncol 24:5552-64 (2006)
DOI:10.1200/JCO.2006.08.2073

PMID:15760280 (carcinogen)

Schottenfeld D, Beebe-Dimmer JL.

Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions.

Annu Rev Public Health 26:37-60 (2005)
DOI:10.1146/annurev.publhealth.26.021304.144402

PMID:9498904 (carcinogen)

Boffetta P, Jourenkova N, Gustavsson P.

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.

Cancer Causes Control 8:444-72 (1997)

PMID:15660110 (carcinogen)

Luch A.

Nature and nurture - lessons from chemical carcinogenesis.

Nat Rev Cancer 5:113-25 (2005)
DOI:10.1038/nrc1546

PMID:11473382 (carcinogen)

Burger MS, Torino JL, Swaminathan S.

DNA damage in human transitional cell carcinoma cells after exposure to the proximate metabolite of the bladder carcinogen 4-aminobiphenyl.

Environ Mol Mutagen 38:1-11 (2001)
DOI:10.1002/em.1044

PMID:14643412 (carcinogen)

Rossman TG.

Mechanism of arsenic carcinogenesis: an integrated approach.

Mutat Res 533:37-65 (2003)
DOI:10.1016/j.mrfmmm.2003.07.009

PMID:9498898 (carcinogen)

Vineis P, Pirastu R.

Aromatic amines and cancer.

Cancer Causes Control 8:346-55 (1997)

PMID:14648102 (carcinogen)

Golka K, Wiese A, Assennato G, Bolt HM.

Occupational exposure and urological cancer.

World J Urol 21:382-91 (2004)
DOI:10.1007/s00345-003-0377-5

PMID:17530489 (carcinogen)

Abnet CC.

Carcinogenic food contaminants.

Cancer Invest 25:189-96 (2007)
DOI:10.1080/07357900701208733

PMID:17195421 (carcinogen)

Olfert SM, Felknor SA, Delclos GL.

An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures.

South Med J 99:1256-63 (2006)
DOI:10.1097/01.smj.0000247266.10393.72

PMID:11886955 (carcinogen)

Verma DK, Purdham JT, Roels HA.

Translating evidence about occupational conditions into strategies for prevention.

Occup Environ Med 59:205-13; quiz 214 (2002)
DOI:10.1136/oem.59.3.156

PMID:12505369 (carcinogen)

Nortier JL, Vanherweghem JL.

Renal interstitial fibrosis and urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi).

Toxicology 181-182:577-80 (2002)
DOI:10.1016/S0300-483X(02)00486-9

PMID:14672753 (carcinogen)

Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ.

Herbal bioactivation: the good, the bad and the ugly.

Life Sci 74:935-68 (2004)
DOI:10.1016/j.lfs.2003.09.035

PMID:10723042 (carcinogen)

Stern FB, Ruder AM, Chen G.

Proportionate mortality among unionized roofers and waterproofers.

Am J Ind Med 37:478-92 (2000)
DOI:10.1002/(SICI)1097-0274(200005)37:5<478::AID-AJIM4>3.0.CO;2-8

PMID:10564925 (carcinogen)

Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H.

Malignancies in patients treated with high doses of radium-224.

Radiat Res 152:S3-7 (1999)
DOI:10.2307/3580102

PMID:15489140 (carcinogen)

Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.

Environmental and chemical carcinogenesis.

Semin Cancer Biol 14:473-86 (2004)
DOI:10.1016/j.semcancer.2004.06.010

PMID:15552776 (carcinogen)

Sasco AJ, Secretan MB, Straif K.

Tobacco smoking and cancer: a brief review of recent epidemiological evidence.

Lung Cancer 45 Suppl 2:S3-9 (2004)
DOI:10.1016/j.lungcan.2004.07.998

PMID:15070562 (carcinogen)

Berrington de Gonzalez A, Darby S.

Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.

Lancet 363:345-51 (2004)
DOI:10.1016/S0140-6736(04)15433-0