KEGG   DISEASE: Colorectal cancerHelp
Entry
H00020                      Disease                                

Name
Colorectal cancer
  Supergrp
Mismatch repair deficiency [DS:H00876]
Description
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as  microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).
Category
Cancer
Brite
Human diseases [BR:br08402]
 Cancers
  Cancers of the digestive system
   H00020  Colorectal cancer
Human diseases in ICD-10 classification [BR:br08403]
 2. Neoplasms (C00-D48)
  C15-C26  Malignant neoplasms of digestive organs
   C18-C20  Malignant neoplasm of colon and rectum
    H00020  Colorectal cancer
Tumor markers [br08442.html]
 H00020
Cancer-accociated carbohydrates [br08441.html]
 H00020
BRITE hierarchy
Pathway
Colorectal cancer
MicroRNAs in cancer
Mucin type O-glycan biosynthesis
Network
N00012  
Mutation-activated KRAS/NRAS to ERK signaling pathway
N00032  
Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00057  
Mutation-inactivated APC to Wnt signaling pathway
N00058  
Mutation-activated CTNNB1 to Wnt signaling pathway
N00064  
Mutation-inactivated TGFBR2 to TGF-beta signaling pathway
N00065  
Mutation-inactivated SMAD2 to TGF-beta signaling pathway
N00099  
Mutation-inactivated BAX to apoptotic pathway
N00102  
Loss of DCC to DCC-apoptotic pathway
N00104  
Mutation-activated KRAS to RalGDS signaling pathway
N00115  
Mutation-inactivated TP53 to transcription
Gene
beta-Catenin (mutation) [HSA:1499] [KO:K02105]
K-ras (mutation) [HSA:3845] [KO:K07827]
APC (germline mutation (FAP), somatic mutation) [HSA:10297] [KO:K02085]
DCC (deletion) [HSA:1630] [KO:K06765]
TGF-betaRII (mutation) [HSA:7048] [KO:K04388]
Smad2 (mutation) [HSA:4087] [KO:K04500]
Smad4 (deletion) [HSA:4089] [KO:K04501]
BAX (mutation) [HSA:581] [KO:K02159]
p53 (deletion) [HSA:7157] [KO:K04451]
MLH1 (germline mutation (HNPCC), LOH, promoter hypermethylation) [HSA:4292] [KO:K08734]
MSH2 (germline mutation (HNPCC), LOH, somatic mutation) [HSA:4436] [KO:K08735]
MSH3 (somatic frameshift mutation) [HSA:4437] [KO:K08736]
MSH6 (germline mutation (HNPCC), LOH, somatic frameshift mutation) [HSA:2956] [KO:K08737]
GALNT12 (germline mutation, somatic mutation) [HSA:79695] [KO:K00710]
Carcinogen
Mineral oils, untreated and mildly treated
X- and gamma-radiation
Drug
Capecitabine [DR:D01223]
Trifluridine - tipiracil hydrochloride mixt [DR:D10526]
Oxaliplatin [DR:D01790]
Cetuximab [DR:D03455] (K-Ras wild type, EGFR-expressing)
Bevacizumab [DR:D06409]
Panitumumab [DR:D05350] (K-Ras wild type)
Nivolumab [DR:D10316]
Pembrolizumab [DR:D10574] (microsatellite instability-high)
Ramucirumab [DR:D09371]
Regorafenib hydrate [DR:D10137]
Irinotecan hydrochloride [DR:D01061]
Aflibercept [DR:D09574]
Leucovorin calcium [DR:D01211]
Levoleucovorin calcium [DR:D04715]
Comment
ICD-O: 8140/3, Tumor type: Adenocarcinoma
Other DBs
ICD-10: 
MeSH: 
Reference
PMID:15000146 (gene, tumor type)
  Authors
Grady WM.
  Title
Genomic instability and colon cancer.
  Journal
Cancer Metastasis Rev 23:11-27 (2004)
DOI:10.1023/A:1025861527711
Reference
PMID:11477132 (tumor type)
  Authors
Houlston RS.
  Title
What we could do now: molecular pathology of colorectal cancer.
  Journal
Mol Pathol 54:206-14 (2001)
DOI:10.1136/mp.54.4.206
Reference
PMID:16555243 (gene)
  Authors
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.
  Title
Microsatellite instability in colorectal cancer.
  Journal
Br J Surg 93:395-406 (2006)
DOI:10.1002/bjs.5328
Reference
PMID:12621137 (gene)
  Authors
Lynch HT, de la Chapelle A.
  Title
Hereditary colorectal cancer.
  Journal
N Engl J Med 348:919-32 (2003)
DOI:10.1056/NEJMra012242
Reference
PMID:15310786 (gene)
  Authors
Mehlen P, Fearon ER.
  Title
Role of the dependence receptor DCC in colorectal cancer pathogenesis.
  Journal
J Clin Oncol 22:3420-8 (2004)
DOI:10.1200/JCO.2004.02.019
Reference
PMID:9498901 (carcinogen)
  Authors
Tolbert PE.
  Title
Oils and cancer.
  Journal
Cancer Causes Control 8:386-405 (1997)
Reference
PMID:15070562 (carcinogen)
  Authors
Berrington de Gonzalez A, Darby S.
  Title
Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries.
  Journal
Lancet 363:345-51 (2004)
DOI:10.1016/S0140-6736(04)15433-0
Reference
(drug)
  Authors
Papadakis MA and McPhee SJ |(ed)
  Title
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition
  Journal
McGraw Hill Education
Reference
PMID:19617566 (gene)
  Authors
Guda K, Moinova H, He J, Jamison O, Ravi L, Natale L, Lutterbaugh J, Lawrence E, Lewis S, Willson JK, Lowe JB, Wiesner GL, Parmigiani G, Barnholtz-Sloan J, Dawson DW, Velculescu VE, Kinzler KW, Papadopoulos N, Vogelstein B, Willis J, Gerken TA, Markowitz SD
  Title
Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers.
  Journal
Proc Natl Acad Sci U S A 106:12921-5 (2009)
DOI:10.1073/pnas.0901454106
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