KEGG   DISEASE: Colorectal cancer
Entry
H00020                      Disease                                
Name
Colorectal cancer
  Subgroup
Familial adenomatous polyposis (FAP) [DS:H01025]
Hereditary nonpolyposis colorectal cancer (HNPCC) [DS:H02565]
Polymerase proofreading-associated polyposis (PPAP) [DS:H02568]
  Supergrp
Solid tumor [DS:H02421]
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-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]
 H00020
Cancer-associated carbohydrates [br08441.html]
 H00020
Pathway
hsa05210  Colorectal cancer
Related
pathway
hsa03430  Mismatch repair
hsa04310  Wnt signaling pathway
hsa05200  Pathways in cancer
hsa05206  MicroRNAs in cancer
Network
nt06260  Colorectal cancer
nt06503  Mismatch repair
Gene
(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]
Carcinogen
Mineral oils, untreated and mildly treated
X- and gamma-radiation
Drug
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]
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
Reference
  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
  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:15000146 (TP53, APC, MSH3, MSH6, CTNNB1, KRAS, TGFBR2, BAX)
  Authors
Grady WM.
  Title
Genomic instability and colon cancer.
  Journal
Cancer Metastasis Rev 23:11-27 (2004)
DOI:10.1023/A:1025861527711
Reference
PMID:16555243 (DCC, SMAD2/4, TP53, APC, MLH1, MSH2, MSH6, CTNNB1, KRAS, TGFBR2, BAX)
  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:15310786 (DCC)
  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:19617566 (GALNT12)
  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
Reference
PMID:17934461 (SNAD7)
  Authors
Broderick P, Carvajal-Carmona L, Pittman AM, Webb E, Howarth K, Rowan A, Lubbe S, Spain S, Sullivan K, Fielding S, Jaeger E, Vijayakrishnan J, Kemp Z, Gorman M, Chandler I, Papaemmanuil E, Penegar S, Wood W, Sellick G, Qureshi M, Teixeira A, Domingo E, Barclay E, Martin L, Sieber O, Kerr D, Gray R, Peto J, Cazier JB, Tomlinson I, Houlston RS
  Title
A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk.
  Journal
Nat Genet 39:1315-7 (2007)
DOI:10.1038/ng.2007.18
Reference
PMID:26133394 (POLE, POLD1)
  Authors
Bellido F, Pineda M, Aiza G, Valdes-Mas R, Navarro M, Puente DA, Pons T, Gonzalez S, Iglesias S, Darder E, Pinol V, Soto JL, Valencia A, Blanco I, Urioste M, Brunet J, Lazaro C, Capella G, Puente XS, Valle L
  Title
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.
  Journal
Genet Med 18:325-32 (2016)
DOI:10.1038/gim.2015.75
Reference
PMID:7912978
  Authors
Hayashi Y, Widjono YW, Ohta K, Hanioka K, Obayashi C, Itoh K, Imai Y, Itoh H
  Title
Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues.
  Journal
Pathol Int 44:124-30 (1994)
DOI:10.1111/j.1440-1827.1994.tb01696.x
Reference
PMID:11017067 (AXIN2)
  Authors
Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, Halling KC, Cunningham JM, Boardman LA, Qian C, Christensen E, Schmidt SS, Roche PC, Smith DI, Thibodeau SN
  Title
Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling.
  Journal
Nat Genet 26:146-7 (2000)
DOI:10.1038/79859
Reference
PMID:12198537 (BRAF, KRAS)
  Authors
Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE
  Title
Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status.
  Journal
Nature 418:934 (2002)
DOI:10.1038/418934a
Reference
PMID:10667569 (CCND1)
  Authors
Kong S, Amos CI, Luthra R, Lynch PM, Levin B, Frazier ML
  Title
Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer.
  Journal
Cancer Res 60:249-52 (2000)
Reference
PMID:12690581 (CHEK2)
  Authors
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
  Title
The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype.
  Journal
Am J Hum Genet 72:1308-14 (2003)
DOI:10.1086/375121
Reference
PMID:12843323 (FLCN)
  Authors
Kahnoski K, Khoo SK, Nassif NT, Chen J, Lobo GP, Segelov E, Teh BT
  Title
Alterations of the Birt-Hogg-Dube gene (BHD) in sporadic colorectal tumours.
  Journal
J Med Genet 40:511-5 (2003)
DOI:10.1136/jmg.40.7.511
Reference
PMID:11317354 (MLH3)
  Authors
Lipkin SM, Wang V, Stoler DL, Anderson GR, Kirsch I, Hadley D, Lynch HT, Collins FS
  Title
Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers.
  Journal
Hum Mutat 17:389-96 (2001)
DOI:10.1002/humu.1114
Reference
PMID:15016963 (PIK3CA)
  Authors
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
  Title
High frequency of mutations of the PIK3CA gene in human cancers.
  Journal
Science 304:554 (2004)
DOI:10.1126/science.1096502
Reference
PMID:21139621 (EGF, TGFA, EREG, AREG)
  Authors
Di Fiore F, Sesboue R, Michel P, Sabourin JC, Frebourg T
  Title
Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer.
  Journal
Br J Cancer 103:1765-72 (2010)
DOI:10.1038/sj.bjc.6606008
Reference
PMID:9521327 (BUB1, BUB1B)
  Authors
Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B
  Title
Mutations of mitotic checkpoint genes in human cancers.
  Journal
Nature 392:300-3 (1998)
DOI:10.1038/32688
Reference
PMID:12881723 (AURKA)
  Authors
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
  Title
Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human.
  Journal
Nat Genet 34:403-12 (2003)
DOI:10.1038/ng1220
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