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).

Cancer

nt06260  Colorectal cancer

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]
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] (MSI-H or dMMR)
Pembrolizumab [DR:D10574] (MSI-H)
Ramucirumab [DR:D09371]
Regorafenib hydrate [DR:D10137]
Encorafenib [DR:D11053] (BRAF mutation positive)
Irinotecan hydrochloride [DR:D01061]
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

PMID:15000146 (gene, tumor type)

Grady WM.

Genomic instability and colon cancer.

Cancer Metastasis Rev 23:11-27 (2004)
DOI:10.1023/A:1025861527711

PMID:11477132 (tumor type)

Houlston RS.

What we could do now: molecular pathology of colorectal cancer.

Mol Pathol 54:206-14 (2001)
DOI:10.1136/mp.54.4.206

PMID:16555243

Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.

Microsatellite instability in colorectal cancer.

Br J Surg 93:395-406 (2006)
DOI:10.1002/bjs.5328

PMID:12621137

Lynch HT, de la Chapelle A.

Hereditary colorectal cancer.

N Engl J Med 348:919-32 (2003)
DOI:10.1056/NEJMra012242

PMID:15310786

Mehlen P, Fearon ER.

Role of the dependence receptor DCC in colorectal cancer pathogenesis.

J Clin Oncol 22:3420-8 (2004)
DOI:10.1200/JCO.2004.02.019

PMID:9498901 (carcinogen)

Tolbert PE.

Oils and cancer.

Cancer Causes Control 8:386-405 (1997)
DOI:10.1023/a:1018409422050

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)
DOI:10.1016/S0140-6736(04)15433-0

(drug)

Papadakis MA and McPhee SJ |(ed)

Current Medical Diagnosis & Treatment 2015, Fifty-Fourth Edition

McGraw Hill Education

PMID:19617566

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)
DOI:10.1073/pnas.0901454106

PMID:7912978

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)
DOI:10.1111/j.1440-1827.1994.tb01696.x

PMID:15668269

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)
DOI:10.1093/annonc/mdi057

PMID:21139621

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)
DOI:10.1038/sj.bjc.6606008

PMID:9815883

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)