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

hsa04310

Wnt signaling pathway

Network

nt06260  Colorectal cancer
nt06503  Mismatch repair
nt06505  WNT signaling
nt06507  TGFB signaling

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]

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

PMID:11477132

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:12621137

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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Gene (62)   
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