KEGG   DISEASE: H00025Help
Entry
H00025                      Disease                                

Name
Penile cancer
Description
Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare in developed countries but more common in South America and East Africa. Squamous cell carcinoma (SCC) is the predominant tumor type in penile cancer, accounting for 95% of cases. Penile cancers are thought to arise from the progression of precursor lesions and can be subdivided into human papilloma virus (HPV) positive and HPV negative cases. Most common disrupted pathways, both in HPV-mediated and HPV-independent penile carcinogenesis, involve the p14ARF/MDM2/p53 and/or p16INK4a/cyclin D/Rb pathways. HPVs exert their oncogenic effect by expressing the oncoproteins E6 and E7, which bind to and inactivate the p53 and Rb tumor suppressor gene products, respectively. HPV independent mechanisms of pathway inactivation include silencing of the p16INK4a gene by promoter hypermethylation, somatic mutations of the p53 gene, over-expression of MDM2 and mutation of p14ARF. Several other molecular events include alterations in the activity and/or expression of ras and myc genes, cyclo-oxygenase-2 (COX) pathway and prostaglandin E2 synthase. These alterations have been described in both HPV-positive and -negative penile cancers.
Category
Cancer
BRITE hierarchy
Pathway
Viral carcinogenesis
Gene
p16/INK4a (promoter hypermethylation) [HSA:1029] [KO:K06621]
BMI1 (overexpression) [HSA:648] [KO:K11459]
p53 (mutation) [HSA:7157] [KO:K04451]
MDM2 (overexpression) [HSA:4193] [KO:K06643]
H-ras (mutation) [HSA:3265] [KO:K02833]
c-MYC (mutation) [HSA:4609] [KO:K04377]
E-Cadherin (expression) [HSA:999] [KO:K05689]
MMP-2 (expression) [HSA:4313] [KO:K01398]
MMP-9 (expression) [HSA:4318] [KO:K01403]
COX-2 (expression) [HSA:5743] [KO:K11987]
PTGES2 (expression) [HSA:80142] [KO:K05309]
Carcinogen
Tobacco smoking and tobacco smoke
Pathogen
Human papillomavirus types 16, 18 [VGNM:NC_001526 NC_001357]
Marker
Human papillomavirus types 16, 18 [VGNM:NC_001526 NC_001357]
Ki-67 [HSA:4288]
p53 [HSA:7157]
E-Cadherin [HSA:999]
Drug
Bleomycin [DR:D02177 D03229]
Cisplatin [DR:D00275]
Methotrexate [DR:D00142 D02115]
Fluorouracil [DR:D00584]
Comment
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:18607597 (description, gene, carcinogen, tumor type)
  Authors
Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ
  Title
Penile cancer: epidemiology, pathogenesis and prevention.
  Journal
World J Urol 27:141-50 (2009)
Reference
PMID:17466899 (gene, carcinogen, tumor type)
  Authors
Kayes O, Ahmed HU, Arya M, Minhas S.
  Title
Molecular and genetic pathways in penile cancer.
  Journal
Lancet Oncol 8:420-9 (2007)
Reference
PMID:18548255 (carcinogen, marker, tumor type)
  Authors
Muneer A, Kayes O, Ahmed HU, Arya M, Minhas S
  Title
Molecular prognostic factors in penile cancer.
  Journal
World J Urol 27:161-7 (2009)
Reference
PMID:11281434 (carcinogen)
  Authors
Severson J, Evans TY, Lee P, Chan T, Arany I, Tyring SK.
  Title
Human papillomavirus infections: epidemiology, pathogenesis, and therapy.
  Journal
J Cutan Med Surg 5:43-60 (2001)
Reference
PMID:1311142 (carcinogen)
  Authors
Daling JR, Sherman KJ, Hislop TG, Maden C, Mandelson MT, Beckmann AM, Weiss NS.
  Title
Cigarette smoking and the risk of anogenital cancer.
  Journal
Am J Epidemiol 135:180-9 (1992)
Reference
PMID:16569359 (marker)
  Authors
Gentile V, Vicini P, Giacomelli L, Cardillo MR, Pierangeli A, Degener AM.
  Title
Detection of human papillomavirus DNA, p53 and ki67 expression in penile carcinomas.
  Journal
Int J Immunopathol Pharmacol 19:209-15 (2006)
Reference
((fifth Japanese edition) drug)
  Authors
Skeel RT (ed).
  Title
Handbook of Cancer Chemotherapy, Sixth Edition
  Journal
Lippincott Williams & Wilkins (2003)

» Japanese version

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