KEGG   DISEASE: Colorectal cancer
H00020                      Disease                                

Colorectal cancer
Mismatch repair deficiency [DS:H00876]
Solid tumor [DS:H02421]
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).
Human diseases [BR:br08402]
  Cancers of the digestive system
   H00020  Colorectal cancer
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
   Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
    Malignant neoplasms of digestive organs
     Malignant neoplasms of intestine
      Malignant neoplasms of large intestine
       2B90  Malignant neoplasms of colon
        H00020  Colorectal cancer
       2B91  Malignant neoplasms of rectosigmoid junction
        H00020  Colorectal cancer
       2B92  Malignant neoplasms of rectum
        H00020  Colorectal cancer
Tumor markers [br08442.html]
Cancer-associated carbohydrates [br08441.html]
hsa05210  Colorectal cancer
hsa05200  Pathways in cancer
hsa05206  MicroRNAs in cancer
nt06260  Colorectal cancer
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00032  Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00041  EGFR-overexpression to RAS-ERK signaling pathway
N00042  EGFR-overexpression 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
N00230  TGFA-overexpression to RAS-ERK signaling pathway
N00232  TGFA-overexpression to PI3K signaling pathway
N00276  EGF-overexpression to RAS-ERK signaling pathway
N00278  EREG-overexpression to RAS-ERK signaling pathway
N00280  AREG-overexpression to RAS-ERK signaling pathway
N00281  EGF-overexpression to PI3K signaling pathway
N00283  EREG-overexpression to PI3K signaling pathway
N00285  AREG-overexpression to PI3K signaling pathway
N01370  PhIP to DNA adducts
N01371  PhIP to DNA adducts
N01373  MeIQx to DNA adducts
N01390  p,p'-DDT to SOD/Cat-mediated ROS neutralization
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]
EGF (overexpression) [HSA:1950] [KO:K04357]
TGFA (overexpression) [HSA:7039] [KO:K08774]
EREG (overexpression) [HSA:2069] [KO:K09784]
AREG (overexpression) [HSA:374] [KO:K09782]
Mineral oils, untreated and mildly treated
X- and gamma-radiation
Capecitabine [DR:D01223]
Floxuridine [DR:D04197]
Trifluridine and tipiracil hydrochloride [DR:D10526]
Irinotecan hydrochloride [DR:D01061]
Encorafenib [DR:D11053] (BRAF mutation positive)
Regorafenib hydrate [DR:D10137]
Oxaliplatin [DR:D01790]
Cetuximab [DR:D03455] (K-Ras wild type, EGFR-expressing)
Bevacizumab [DR:D06409]
Panitumumab [DR:D05350] (KRAS and NRAS wild type)
Nivolumab [DR:D10316] (MSI-H or dMMR)
Pembrolizumab [DR:D10574] (MSI-H)
Ramucirumab [DR:D09371]
Aflibercept [DR:D09574]
Leucovorin calcium [DR:D01211]
Levoleucovorin calcium [DR:D04715]
Calcium levofolinate hydrate [DR:D11555]
Sodium levofolinate [DR:D11394]
ICD-O: 8140/3, Tumor type: Adenocarcinoma
Other DBs
ICD-11: 2B90 2B91 2B92
ICD-10: C18 C19 C20
MeSH: D015179
PMID:15000146 (gene, tumor type)
Grady WM.
Genomic instability and colon cancer.
Cancer Metastasis Rev 23:11-27 (2004)
PMID:11477132 (tumor type)
Houlston RS.
What we could do now: molecular pathology of colorectal cancer.
Mol Pathol 54:206-14 (2001)
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.
Microsatellite instability in colorectal cancer.
Br J Surg 93:395-406 (2006)
Lynch HT, de la Chapelle A.
Hereditary colorectal cancer.
N Engl J Med 348:919-32 (2003)
Mehlen P, Fearon ER.
Role of the dependence receptor DCC in colorectal cancer pathogenesis.
J Clin Oncol 22:3420-8 (2004)
PMID:9498901 (carcinogen)
Tolbert PE.
Oils and cancer.
Cancer Causes Control 8:386-405 (1997)
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)
Papadakis MA and McPhee SJ |(ed)
Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition
McGraw Hill Education
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
Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers.
Proc Natl Acad Sci U S A 106:12921-5 (2009)
Hayashi Y, Widjono YW, Ohta K, Hanioka K, Obayashi C, Itoh K, Imai Y, Itoh H
Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues.
Pathol Int 44:124-30 (1994)
Spano JP, Fagard R, Soria JC, Rixe O, Khayat D, Milano G
Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives.
Ann Oncol 16:189-94 (2005)
Di Fiore F, Sesboue R, Michel P, Sabourin JC, Frebourg T
Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer.
Br J Cancer 103:1765-72 (2010)
Radinsky R, Risin S, Fan D, Dong Z, Bielenberg D, Bucana CD, Fidler IJ
Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells.
Clin Cancer Res 1:19-31 (1995)

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