Genetics of colonic cancer

Digestion. 1998 Aug;59(5):481-92. doi: 10.1159/000007525.


Research in hereditary forms of colorectal cancer (CRC) has increased almost logarithmically thanks in a major way to momentous discoveries in molecular genetics during the past decade. Between 10 and 20% of the total CRC burden is due to Mendelian-inherited CRC syndromes. The paradigm for hereditary CRC is familial adenomatous polyposis (FAP), wherein the APC germ-line mutation has been identified. This has contributed to the elucidation of genomic and clinical heterogeneity within the syndrome, wherein an attenuated form of FAP has been identified as a result of intragenic mutations within this large APC gene. The most common form of hereditary CRC is hereditary nonpolyposis colorectal cancer (HNPCC). Several mutator genes, namely hMSH2, hMLH1, hPMS1, hPMS2 and, more recently, hMSH6/GTBP, have been identified. These molecular genetic discoveries are providing new insights into the pathogenesis of CRC. Individuals within these kindreds who are harbingers of these germ-line mutations will benefit from screening and, one day, chemoprevention.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adenomatous Polyposis Coli / diagnosis
  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / prevention & control
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / prevention & control
  • Colorectal Neoplasms, Hereditary Nonpolyposis / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / prevention & control
  • Cyclooxygenase Inhibitors / therapeutic use
  • Diagnosis, Differential
  • Genes, Tumor Suppressor / genetics
  • Humans
  • Peutz-Jeghers Syndrome / diagnosis
  • Peutz-Jeghers Syndrome / genetics
  • Peutz-Jeghers Syndrome / prevention & control
  • Phenotype


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors