Advertisement

Pathogenesis of Colorectal Cancer

  • Adam I. Cygankiewicz
  • Damian Jacenik
  • Wanda M. Krajewska
Chapter

Abstract

Colorectal cancer, because of its high morbidity and mortality rates, is one of the most studied human diseases. Advances in our understanding of the molecular genetics and epigenetics of colorectal cancer have led to novel insights into its pathogenesis. The results show that both pathogenic mechanisms and the influence of the etiological factors create a complex and multifarious network of events. Somatic and germline mutations, alongside with chromosomal and microsatellite instability, and epigenetic changes were found to be the key factors in both heritable and sporadic cases of colorectal cancer.

Keywords

Colorectal cancer Hereditary colorectal cancer Colonic polyps Somatic mutations Germline mutations Microsatellite instability Chromosomal instability Epigenetics 

Abbreviations

APC

Adenomatous polyposis coli

BAX

Bcl-2-associated X protein

BRAF

v-Raf murine sarcoma viral oncogene homologue B

CABLES

CDK5 and ABL1 enzyme substrate 1 gene

CDK

Cyclin-dependent cell cycle kinase

CDKN2A

Cyclin-dependent kinase inhibitor 2A

CIMP

CpG island methylator phenotype

CIN

Chromosome instability

CpG

5′-Cytosine-phosphate-guanine-3′ sequence

CRC

Colorectal cancer

DCC

Deleted in colorectal cancer

FAP

Familial adenomatous polyposis

GATA

Transcription factor

GTP

Guanidine tri-phosphate

HDAC2

Phosphatase and tensin homologue

HIC1

Hypermethylated in cancer 1

HMPS

Hereditary mixed polyposis syndrome

HNPCC

Hereditary nonpolyposis colorectal cancer

IGF

Insulin-like growth factor

JPS

Juvenile polyposis syndrome

KRAS

Kirsten rat sarcoma 2 viral oncogene homologue

LOH

Loss of heterozygosity

MAP

MUTYH-associated polyposis

MGMT

O-6-methylguanine-DNA methyltransferase

MINT

Methylated in tumor

miRNA

Micro-RNA

MLH

MutL homologue

MMR

DNA mismatch repair

MRE11A

Meiotic recombination 11 homologue A

MSH

MutS homologue

MSI

Microsatellite instability

MSS

Microsatellite stable

MUTYH

MutY homologue

MYC

Avian myelocytomatosis viral oncogene homologue

PJS

Peutz-Jeghers syndrome

PMS

Postmeiotic segregation increased

POLE/POLD1

Polymerase proofreading-associated polyposis

PTEN

Phosphatase and tensin homologue

RAD50

S. cerevisiae and D. melanogaster homologue

RAS

Rat sarcoma viral oncogene homologue

RUNX3

Runt-related transcription factor 3

SMAD

Mothers against decapentaplegic homologue

SOCS1

Suppressor of cytokine signaling 1

SPS

Serrated polyposis syndrome

SRFP

Secreted frizzled-related protein 1

TGFβ

Transforming growth factor β

TIMP3

Tissue inhibitor of metalloproteinase 3

TP53

Tumor protein p53/tumor suppressor p53

Wnt

Wingless-related integration site

References

  1. 1.
    Ervik M, Lam F, Ferlay J, Mery L, Soerjomataram I, Bray F. Cancer today. Lyon, France: International Agency for Research on Cancer; 2016. Available from: http://gco.iarc.fr/today. Accessed 19 Nov 2016Google Scholar
  2. 2.
    Shiller M, Boostrom S. The molecular basis of rectal cancer. Clin Colon Rectal Surg. 2015;28(1):53–60. doi: 10.1055/s-0035-1545070.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hardy RG, Meltzer SJ, Jankowski JA. ABC of colorectal cancer. Molecular basis for risk factors. BMJ. 2000;321(7265):886–9.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    de la Chapelle A. Genetic predisposition to colorectal cancer. Nat Rev Cancer. 2004;4(10):769–80.CrossRefPubMedGoogle Scholar
  5. 5.
    Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61(5):759–67.CrossRefPubMedGoogle Scholar
  6. 6.
    Worthley DL, Whitehall VL, Spring KJ, Leggett BA. Colorectal carcinogenesis: road maps to cancer. World J Gastroenterol. 2007;13(28):3784–91.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361(25):2449–60. doi: 10.1056/NEJMra0804588.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Al-Sohaily S, Biankin A, Leong R, Kohonen-Corish M, Warusavitarne J. Molecular pathways in colorectal cancer. J Gastroenterol Hepatol. 2012;27(9):1423–31. doi: 10.1111/j.1440-1746.2012.07200.x.CrossRefPubMedGoogle Scholar
  9. 9.
    Schweiger MR, Hussong M, Röhr C, Lehrach H. Genomics and epigenomics of colorectal cancer. Wiley Interdiscip Rev Syst Biol Med. 2013;5(2):205–19. doi: 10.1002/wsbm.1206.CrossRefPubMedGoogle Scholar
  10. 10.
    Gregorieff A, Clevers H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 2005;19(8):877–90.CrossRefPubMedGoogle Scholar
  11. 11.
    Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol. 2011;6:479–507. doi: 10.1146/annurev-pathol-011110-130235.CrossRefPubMedGoogle Scholar
  12. 12.
    Perea J, Lomas M, Hidalgo M. Molecular basis of colorectal cancer: towards an individualized management? Rev Esp Enferm Dig. 2011;103(1):29–35.CrossRefPubMedGoogle Scholar
  13. 13.
    Vilar E, Gruber SB. Microsatellite instability in colorectal cancer-the stable evidence. Nat Rev Clin Oncol. 2010;7(3):153–62. doi: 10.1038/nrclinonc.2009.237.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wajed SA, Laird PW, DeMeester TR. DNA methylation: an alternative pathway to cancer. Ann Surg. 2001;234(1):10–20.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004;4(12):988–93.CrossRefPubMedGoogle Scholar
  16. 16.
    Wong JJ, Hawkins NJ, Ward RL. Colorectal cancer: a model for epigenetic tumorigenesis. Gut. 2007;56(1):140–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Arends MJ. Pathways of colorectal carcinogenesis. Appl Immunohistochem Mol Morphol. 2013;21(2):97–102. doi: 10.1097/PAI.0b013e31827ea79e.PubMedGoogle Scholar
  18. 18.
    Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009;8:102. doi: 10.1186/1476-4598-8-102.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Adam I. Cygankiewicz
    • 1
  • Damian Jacenik
    • 1
  • Wanda M. Krajewska
    • 1
  1. 1.Department of Cytobiochemistry, Faculty of Biology and Environmental ProtectionUniversity of LodzLodzPoland

Personalised recommendations