KEGG   DISEASE: H00048Help
Entry
H00048                      Disease                                

Name
Hepatocellular carcinoma
Description
Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been implicated in about 80% of cases worldwide, and other known environmental risk factors, including alcohol abuse and dietary intake of aflatoxin B1, might synergize with viral infections. Recent studies have discovered genetic and epigenetic changes involved in the molecular pathogenesis of HCC, including mutations in Rb1, AXIN1, p53, IGFR-II/M6PR, p16, E-Cadherin, and PTEN. The most frequently mutated genes in HCC include p53 and beta-catenin, although mutation prevalence varies greatly depending on etiology.
Category
Cancer
BRITE hierarchy
Pathway
Viral carcinogenesis
MicroRNAs in cancer
Gene
PTEN (mutation) [HSA:5728] [KO:K01110]
H-ras (mutation) [HSA:3265] [KO:K02833]
K-ras (mutation) [HSA:3845] [KO:K07827]
N-ras (mutation) [HSA:4893] [KO:K07828]
AXIN1 (mutation) [HSA:8312] [KO:K02157]
beta-Catenin (mutation) [HSA:1499] [KO:K02105]
p53 (mutation) [HSA:7157] [KO:K04451]
p73 (mutation) [HSA:7161] [KO:K10148]
RB1 (mutation) [HSA:5925] [KO:K06618]
p16/INK4A (mutation) [HSA:1029] [KO:K06621]
E-Cadherin (mutation) [HSA:999] [KO:K05689]
IGF2R (mutation) [HSA:3482] [KO:K06564]
Carcinogen
Aflatoxins (naturally occurring mixtures of) [CPD:C06800]
Alcoholic beverages
Opisthorchis viverrini (infection with)
Radium-224 and its decay products [CPD:C16455]
*Chimney sweeping
*2,3,7,8-Tetrachlorodibenzo-para-dioxin [CPD:C07557]
*Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium232 dioxide
*Tobacco smoking and tobacco smoke
*: Although this is a risk factor for liver cancer in general, the strength of association with different histological tumor types is not well understood.
Pathogen
Hepatitis B virus (chronic infection with) [VGNM:NC_003977]
Hepatitis C virus (chronic infection with) [VGNM:NC_004102]
Marker
AFP [HSA:174]
AFP-L3 (LCA-bound fraction, the major glycoform of AFP)
DCP (PIVKA-II)
Glypican-3 [HSA:2719]
HS-GGT [HSA:2678]
TGF-beta1 [HSA:7040]
Drug
Doxorubicin [DR:D03899 D01275]
Comment
ICD-O: 8170/3, Tumor type: Hepatocellular carcinoma (liver cell carcinoma)
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:17295177 (gene, tumor type)
  Authors
Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM.
  Title
Genomics and signaling pathways in hepatocellular carcinoma.
  Journal
Semin Liver Dis 27:55-76 (2007)
Reference
PMID:11935086 (gene, tumor type)
  Authors
Rocken C, Carl-McGrath S.
  Title
Pathology and pathogenesis of hepatocellular carcinoma.
  Journal
Dig Dis 19:269-78 (2001)
Reference
PMID:17051452 (marker, tumor type)
  Authors
Spangenberg HC, Thimme R, Blum HE.
  Title
Serum markers of hepatocellular carcinoma.
  Journal
Semin Liver Dis 26:385-90 (2006)
Reference
PMID:12149612 (gene)
  Authors
Thorgeirsson SS, Grisham JW.
  Title
Molecular pathogenesis of human hepatocellular carcinoma.
  Journal
Nat Genet 31:339-46 (2002)
Reference
PMID:15760280 (carcinogen)
  Authors
Schottenfeld D, Beebe-Dimmer JL.
  Title
Advances in cancer epidemiology: understanding causal mechanisms and the evidence for implementing interventions.
  Journal
Annu Rev Public Health 26:37-60 (2005)
Reference
PMID:15757802 (carcinogen)
  Authors
McGlynn KA, London WT.
  Title
Epidemiology and natural history of hepatocellular carcinoma.
  Journal
Best Pract Res Clin Gastroenterol 19:3-23 (2005)
Reference
PMID:15489140 (carcinogen)
  Authors
Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
  Title
Environmental and chemical carcinogenesis.
  Journal
Semin Cancer Biol 14:473-86 (2004)
Reference
PMID:11285186 (carcinogen)
  Authors
Smela ME, Currier SS, Bailey EA, Essigmann JM.
  Title
The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis.
  Journal
Carcinogenesis 22:535-45 (2001)
Reference
PMID:15928434 (carcinogen)
  Authors
Khurana S, Dubey ML, Malla N.
  Title
Association of parasitic infections and cancers.
  Journal
Indian J Med Microbiol 23:74-9 (2005)
Reference
PMID:10564925 (carcinogen)
  Authors
Nekolla EA, Kellerer AM, Kuse-Isingschulte M, Eder E, Spiess H.
  Title
Malignancies in patients treated with high doses of radium-224.
  Journal
Radiat Res 152:S3-7 (1999)
Reference
PMID:9498904 (carcinogen)
  Authors
Boffetta P, Jourenkova N, Gustavsson P.
  Title
Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons.
  Journal
Cancer Causes Control 8:444-72 (1997)
Reference
PMID:15660110 (carcinogen)
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
Reference
PMID:12556326 (carcinogen)
  Authors
Harrison JD, Muirhead CR.
  Title
Quantitative comparisons of cancer induction in humans by internally deposited radionuclides and external radiation.
  Journal
Int J Radiat Biol 79:1-13 (2003)
Reference
PMID:17548245 (marker)
  Authors
Yao DF, Dong ZZ, Yao M.
  Title
Specific molecular markers in hepatocellular carcinoma.
  Journal
Hepatobiliary Pancreat Dis Int 6:241-7 (2007)
Reference
PMID:16534867 (marker)
  Authors
Zhou L, Liu J, Luo F.
  Title
Serum tumor markers for detection of hepatocellular carcinoma.
  Journal
World J Gastroenterol 12:1175-81 (2006)
Reference
(drug)
  Authors
Skeel RT (ed).
  Title
Handbook of Cancer Chemotherapy, Sixth Edition
  Journal
Lippincott Williams & Wilkins (2003)

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