KEGG   DISEASE: H00025Help
H00025                      Disease                                

Penile cancer
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.
Human diseases [BR:br08402]
  Cancers of the urinary system and male genital organs
   H00025  Penile cancer
Human diseases in ICD-10 classification [BR:br08403]
 2. Neoplasms (C00-D48)
  C60-C63  Malignant neoplasms of male genital organs
   C60  Malignant neoplasm of penis
    H00025  Penile cancer
BRITE hierarchy
Viral carcinogenesis
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]
Tobacco smoking and tobacco smoke
Human papillomavirus types 16, 18 [RS:NC_001526 NC_001357]
Human papillomavirus types 16, 18
Ki-67 [HSA:4288]
p53 [HSA:7157]
E-Cadherin [HSA:999]
Bleomycin [DG:DG00705]
Cisplatin [DR:D00275]
Methotrexate [DG:DG00681]
Fluorouracil [DG:DG00687]
ICD-O: 8070/3, Tumor type: Squamous cell carcinoma
Other DBs
PMID:18607597 (description, gene, carcinogen, tumor type)
Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ
Penile cancer: epidemiology, pathogenesis and prevention.
World J Urol 27:141-50 (2009)
PMID:17466899 (gene, carcinogen, tumor type)
Kayes O, Ahmed HU, Arya M, Minhas S.
Molecular and genetic pathways in penile cancer.
Lancet Oncol 8:420-9 (2007)
PMID:18548255 (carcinogen, marker, tumor type)
Muneer A, Kayes O, Ahmed HU, Arya M, Minhas S
Molecular prognostic factors in penile cancer.
World J Urol 27:161-7 (2009)
PMID:11281434 (carcinogen)
Severson J, Evans TY, Lee P, Chan T, Arany I, Tyring SK.
Human papillomavirus infections: epidemiology, pathogenesis, and therapy.
J Cutan Med Surg 5:43-60 (2001)
PMID:1311142 (carcinogen)
Daling JR, Sherman KJ, Hislop TG, Maden C, Mandelson MT, Beckmann AM, Weiss NS.
Cigarette smoking and the risk of anogenital cancer.
Am J Epidemiol 135:180-9 (1992)
PMID:16569359 (marker)
Gentile V, Vicini P, Giacomelli L, Cardillo MR, Pierangeli A, Degener AM.
Detection of human papillomavirus DNA, p53 and ki67 expression in penile carcinomas.
Int J Immunopathol Pharmacol 19:209-15 (2006)
((fifth Japanese edition) drug)
Skeel RT (ed).
Handbook of Cancer Chemotherapy, Sixth Edition
Lippincott Williams & Wilkins (2003)

» Japanese version

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