KEGG   DISEASE: Colorectal cancer
H00020                      Disease                                
Colorectal cancer
Familial adenomatous polyposis (FAP) [DS:H01025]
Hereditary nonpolyposis colorectal cancer (HNPCC) [DS:H02565]
Polymerase proofreading-associated polyposis (PPAP) [DS:H02568]
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 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
Pathway-based classification of diseases [BR:br08402]
 Replication and repair
  nt06503  Mismatch repair
   H00020  Colorectal cancer
 Signal transduction
  nt06526  MAPK signaling
   H00020  Colorectal cancer
  nt06505  WNT signaling
   H00020  Colorectal cancer
  nt06507  TGFB signaling
   H00020  Colorectal cancer
 Cellular process
  nt06515  Regulation of kinetochore-microtubule interactions
   H00020  Colorectal cancer
  nt06524  Apoptosis
   H00020  Colorectal cancer
Tumor markers [br08442.html]
Cancer-associated carbohydrates [br08441.html]
hsa05210  Colorectal cancer
hsa04310  Wnt signaling pathway
hsa04350  TGF-beta signaling pathway
hsa04210  Apoptosis
nt06260 Colorectal cancer
nt06503 Mismatch repair
nt06505 WNT signaling
nt06507 TGFB signaling
nt06515 Regulation of kinetochore-microtubule interactions
nt06524 Apoptosis
(HNPCC) MLH1 [HSA:4292] [KO:K08734]
(HNPCC) MLH3 [HSA:27030] [KO:K08739]
(HNPCC) MSH2 [HSA:4436] [KO:K08735]
(HNPCC) MSH6 [HSA:2956] [KO:K08737]
(HNPCC) TGFBR2 [HSA:7048] [KO:K04388]
(FAP) APC [HSA:324] [KO:K02085]
(FAP) MSH3 [HSA:4437] [KO:K08736]
(PPAP) POLD1 [HSA:5424] [KO:K02327]
(PPAP) POLE [HSA:5426] [KO:K02324]
DCC [HSA:1630] [KO:K06765]
KRAS [HSA:3845] [KO:K07827]
GALNT12 [HSA:79695] [KO:K00710]
SMAD7 [HSA:4092] [KO:K19631]
SMAD4 [HSA:4089] [KO:K04501]
SMAD2 [HSA:4087] [KO:K04500]
BAX [HSA:581] [KO:K02159]
AXIN2 [HSA:8313] [KO:K04385]
BRAF [HSA:673] [KO:K04365]
CCND1 [HSA:595] [KO:K04503]
CHEK2 [HSA:11200] [KO:K06641]
CTNNB1 [HSA:1499] [KO:K02105]
FLCN [HSA:201163] [KO:K09594]
PIK3CA [HSA:5290] [KO:K00922]
TP53 [HSA:7157] [KO:K04451]
BUB1 [HSA:699] [KO:K02178]
BUB1B [HSA:701] [KO:K06637]
AURKA [HSA:6790] [KO:K11481]
EGF (overexpression) [HSA:1950] [KO:K04357]
TGFA (overexpression) [HSA:7039] [KO:K08774]
EREG (overexpression) [HSA:2069] [KO:K09784]
AREG (overexpression) [HSA:374] [KO:K09782]
Capecitabine [DR:D01223]
Floxuridine [DR:D04197]
Trifluridine and tipiracil hydrochloride [DR:D10526]
Irinotecan hydrochloride [DR:D01061]
Encorafenib [DR:D11053] (BRAF mutation positive)
Fruquintinib [DR:D11977]
Regorafenib hydrate [DR:D10137]
Cetuximab [DR:D03455] (BRAF mutation positive)
Panitumumab [DR:D05350] (KRAS and NRAS wild type)
Nivolumab [DR:D10316] (MSI-H or dMMR)
Pembrolizumab [DR:D10574] (MSI-H)
Bevacizumab [DR:D06409]
Ramucirumab [DR:D09371]
Oxaliplatin [DR:D01790]
Aflibercept [DR:D09574]
Leucovorin calcium [DR:D01211]
Levoleucovorin calcium [DR:D04715]
Calcium levofolinate hydrate [DR:D11555]
Sodium levofolinate [DR:D11394]
Other DBs
ICD-11: 2B90 2B91 2B92
ICD-10: C18 C19 C20
MeSH: D015179
OMIM: 114500 608812 612229
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Hereditary colorectal cancer.
N Engl J Med 348:919-32 (2003)
PMID:15000146 (TP53, APC, MSH3, MSH6, CTNNB1, KRAS, TGFBR2, BAX)
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Genomic instability and colon cancer.
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PMID:16555243 (DCC, SMAD2/4, TP53, APC, MLH1, MSH2, MSH6, CTNNB1, KRAS, TGFBR2, BAX)
Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.
Microsatellite instability in colorectal cancer.
Br J Surg 93:395-406 (2006)
PMID:15310786 (DCC)
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Role of the dependence receptor DCC in colorectal cancer pathogenesis.
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PMID:19617566 (GALNT12)
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A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk.
Nat Genet 39:1315-7 (2007)
PMID:26133394 (POLE, POLD1)
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POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance.
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Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues.
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PMID:11017067 (AXIN2)
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Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling.
Nat Genet 26:146-7 (2000)
PMID:12198537 (BRAF, KRAS)
Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE
Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.
Nature 418:934 (2002)
PMID:10667569 (CCND1)
Kong S, Amos CI, Luthra R, Lynch PM, Levin B, Frazier ML
Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer.
Cancer Res 60:249-52 (2000)
PMID:12690581 (CHEK2)
Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, Hollestelle A, Elstrodt F, van den Bos R, de Snoo A, Fat GT, Brekelmans C, Jagmohan S, Franken P, Verkuijlen P, van den Ouweland A, Chapman P, Tops C, Moslein G, Burn J, Lynch H, Klijn J, Fodde R, Schutte M
The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype.
Am J Hum Genet 72:1308-14 (2003)
PMID:12843323 (FLCN)
Kahnoski K, Khoo SK, Nassif NT, Chen J, Lobo GP, Segelov E, Teh BT
Alterations of the Birt-Hogg-Dube gene (BHD) in sporadic colorectal tumours.
J Med Genet 40:511-5 (2003)
PMID:11317354 (MLH3)
Lipkin SM, Wang V, Stoler DL, Anderson GR, Kirsch I, Hadley D, Lynch HT, Collins FS
Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers.
Hum Mutat 17:389-96 (2001)
PMID:15016963 (PIK3CA)
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE
High frequency of mutations of the PIK3CA gene in human cancers.
Science 304:554 (2004)
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)
PMID:9521327 (BUB1, BUB1B)
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B
Mutations of mitotic checkpoint genes in human cancers.
Nature 392:300-3 (1998)
PMID:12881723 (AURKA)
Ewart-Toland A, Briassouli P, de Koning JP, Mao JH, Yuan J, Chan F, MacCarthy-Morrogh L, Ponder BA, Nagase H, Burn J, Ball S, Almeida M, Linardopoulos S, Balmain A
Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human.
Nat Genet 34:403-12 (2003)

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