Pathology and genetics of hereditary colorectal cancer

Pathology. 2018 Jan;50(1):49-59. doi: 10.1016/j.pathol.2017.09.004. Epub 2017 Nov 21.


Colorectal cancer (CRC) accounts for over 8% of all deaths annually worldwide. Between 2 and 5% of all CRCs occur due to inherited syndromes, including Lynch syndrome, familial adenomatous polyposis, MUTYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis and Cowden/PTEN hamartoma syndrome. In addition, serrated polyposis is a clinically defined condition characterised by multiple colorectal serrated polyps and an increased risk of CRC but the genetics are not known. In most hereditary CRC syndromes, polyps undergo carcinogenesis, but the exact route to carcinoma seems to differ between the conditions. Discovery of the key germline mutations in these syndromes has been instrumental to our understanding of the underlying molecular mechanisms of colorectal carcinogenesis. This review summarises the genetic and pathological alterations in hereditary CRC syndromes.

Keywords: AFAP; CS; Cowden syndrome; FAP; Familial colon cancer; JPS; LS; Lynch syndrome; MAP; MUTYH-associated polyposis; PJS; Peutz–Jeghers syndrome; SPS; attenuated familial adenomatous polyposis; familial adenomatous polyposis; genetic defect; hereditary polyposis syndrome; juvenile polyposis syndrome; serrated polyposis syndrome.

Publication types

  • Review

MeSH terms

  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / pathology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Germ-Line Mutation
  • Humans
  • Intestinal Polyposis / congenital*
  • Intestinal Polyposis / genetics
  • Intestinal Polyposis / pathology
  • Neoplastic Syndromes, Hereditary / genetics*
  • Neoplastic Syndromes, Hereditary / pathology
  • Peutz-Jeghers Syndrome / genetics*
  • Peutz-Jeghers Syndrome / pathology

Supplementary concepts

  • Juvenile polyposis syndrome