Lynch Syndrome (Hereditary Non-Polyposis Colon Cancer)

Lynch syndrome has returned to the favoured description due to the multiple non-colon cancers that can develop as a result of microsatellite instability.


Lynch syndrome is due to germline mutation in one of a number of DNA mismatch repair genes (MSH2, MSH6, MLH1, PMS1 and PMS2). When the corresponding normal gene is also lost, microsatellite instability can develop. Microsatellites are regions of dinucleotide repeats (eg. CACACACACACACA) that can be found throughout the genome; their true purpose is not known but errors in transcription are proposed to lead to errors in tumour suppressor genes, maybe due to frameshift mutation. This microsatellite instability can be detected on genetic tests in the pathology lab.

Clinical Features

The features are highly dependent on the mutation; MSH6 appears to be the most carcinogenic for endometrial cancer for instance.
About 70% of patients will develop colon cancer, often at a younger age than sporadic forms of the disease (mean age 45 instead of 65). The progression from adenoma to carcinoma is thought to be more rapid, meaning more regular colonoscopies are required. Lesions frequently develop in the proximal large bowel.
Up to 70% of women will develop endometrial cancer, again at a younger age than sporadic forms (55 instead of 65).
A number of other cancers are also at increased risk of developing with a risk of about 2-5%, including:

  • Glioma
  • Gastric cancer
  • Ovarian cancer
  • Urothelial cancer
  • Small bowel cancer


Patients should have annual colonoscopy starting at age 25; the rapid growth of tumours from normal appearing epithlium means that longer intervals are potentially dangerous. The appropriate treatment once a tumour has developed is controversial; either total colectomy or hemicolectomy are considered reasonable.
Extra-colonic cancer management and prevention varies by site and is not evidence based:

  • Women should undergo regular ultrasound, endometrial biopsy, and vaginal examination after the age of 30
  • Gastroscopy should be considered every few years
  • Annual skin check
  • Iron and full blood count with small bowel evaluation (eg. pill cam) if abnormal
  • Urine cytology is controversial due to low sensitivity and specificity