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# Lynch syndrome (hereditary non-polyposis colorectal cancer)

An inherited tendency to colon, endometrial and other cancers caused by faults in the genes that fix copying errors in DNA.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Ascending colon](https://durgical.com/en/anatomy/ascending-colon/)
- [Cecum](https://durgical.com/en/anatomy/cecum/)
- [Endometrium](https://durgical.com/en/anatomy/endometrium/)
- [Transverse colon](https://durgical.com/en/anatomy/transverse-colon/)
- [Descending colon](https://durgical.com/en/anatomy/descending-colon/)
- [Sigmoid colon](https://durgical.com/en/anatomy/sigmoid-colon/)
- [Stomach](https://durgical.com/en/anatomy/stomach/)
- [Ovaries](https://durgical.com/en/anatomy/ovary/)
- [Rectum](https://durgical.com/en/anatomy/rectum/)
- [Urinary bladder](https://durgical.com/en/anatomy/urinary-bladder/)

## In biochemistry

- [DNA repair](https://durgical.com/en/biochemistry/topics/dna-repair/)
- [DNA sequencing](https://durgical.com/en/biochemistry/topics/dna-sequencing/)

## In the clinical exam

- [Past medical, surgical, family and social history](https://durgical.com/en/clinical-exam/past-medical-surgical-family-and-social-history/)

## Why it happens

- [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/)
- [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/)
- [Multistep carcinogenesis: the adenoma–carcinoma sequence](https://durgical.com/en/general-pathology/multistep-carcinogenesis-the-adenoma-carcinoma-sequence/)
- [How tumours evade the immune system](https://durgical.com/en/general-pathology/how-tumours-evade-the-immune-system/)
- [Molecular pathology: PCR, FISH, sequencing and liquid biopsy](https://durgical.com/en/general-pathology/molecular-pathology-pcr-fish-sequencing-and-liquid-biopsy/)
- [The hallmarks of cancer](https://durgical.com/en/general-pathology/the-hallmarks-of-cancer/)

## Show 2 more

- [Translocations, amplifications and epigenetic changes in cancer](https://durgical.com/en/general-pathology/translocations-amplifications-and-epigenetic-changes-in-cancer/)
- [Immunohistochemistry: the principle and the markers to know](https://durgical.com/en/general-pathology/immunohistochemistry-the-principle-and-the-markers-to-know/)

## What it is

An autosomal dominant syndrome caused by a germline variant in a mismatch repair gene (MLH1, MSH2, MSH6, PMS2) or an EPCAM deletion that silences MSH2.

## Who gets it

It is the most common hereditary colorectal cancer syndrome: in the United States about 1 in 279 people is estimated to carry an associated variant. It explains about 3% of colorectal cancers. Families have been described in Colombia in hereditary cancer studies, but there is no population figure.

## Causes

- Inherited pathogenic variant in MLH1, MSH2, MSH6 or PMS2
- 3' EPCAM deletion that methylates and silences MSH2
- The second copy is lost in the tissue (two-hit model)

## Risk factors

- Relatives with early colorectal or endometrial cancer
- Several associated cancers in one person or family
- Amsterdam II or Bethesda criteria

## Pathophysiology

The carrier's cells have one working MMR gene copy; once they lose it (second hit), DNA polymerase errors are no longer corrected. Microsatellites change length (microsatellite instability) and frameshift mutations build up in repeat-containing genes such as TGFBR2 and BAX. This speeds up the adenoma–carcinoma sequence: an adenoma can turn into cancer in 2–3 years. The tumours are hypermutated, highly immunogenic and full of lymphocytes.

## Classification

- By gene: MLH1 and MSH2 (highest risk), MSH6 (more endometrial risk), PMS2 (lower risk)
- Muir-Torre syndrome: Lynch with sebaceous tumours
- Turcot syndrome (variant): with brain tumours

## Symptoms and signs

- Often no symptoms until a cancer appears
- Rectal bleeding, iron-deficiency anaemia or change in bowel habit
- Abnormal or postmenopausal uterine bleeding
- Abdominal pain or weight loss

## Red flags

- Rectal bleeding or iron-deficiency anaemia in a young person
- Postmenopausal bleeding
- Bowel obstruction

## Diagnosis

**Clinical**
Suspected from family history (Amsterdam II or Bethesda criteria) or from colorectal or endometrial cancer before age 50.

**Tests**
In every colorectal and endometrial cancer: immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 or microsatellite instability testing; if MLH1 is lost, look for a BRAF mutation or promoter methylation (sporadic cause); confirm with germline genetic testing.

**Imaging**
Colonoscopy finds and removes polyps; CT stages the cancer.

## Treatment

**Follow-up**
Regular colonoscopy from early adulthood, at short intervals set by the affected gene.

**Surgical**
Colectomy (sometimes extended) when cancer appears; risk-reducing hysterectomy and salpingo-oophorectomy once childbearing is complete, depending on the gene.

**Medical**
Long-term aspirin lowers colorectal cancer risk in carriers (an individual decision with the specialist).

**Medical**
MMR-deficient tumours often respond to immune checkpoint inhibitors.

**Follow-up**
Cascade testing of first-degree relatives and genetic counselling.

## Complications

- Colorectal cancer (mainly right colon)
- Endometrial and ovarian cancer
- Cancers of the [stomach](https://durgical.com/en/anatomy/stomach/), small bowel, urinary tract, bile ducts and [pancreas](https://durgical.com/en/anatomy/pancreas/)
- Sebaceous [skin](https://durgical.com/en/anatomy/skin/) tumours

## Prognosis

Colonoscopic surveillance markedly lowers colorectal cancer deaths; MMR-deficient cancers have, stage for stage, a better outlook than sporadic ones.

## Prevention

- Surveillance colonoscopy in carriers
- Risk-reducing gynaecological surgery in selected carriers
- Genetic counselling and testing of relatives

## Test yourself

Think of the answer, then tap the question to see it.

## Which DNA repair system fails in Lynch syndrome?

Mismatch repair (MMR): the MLH1, MSH2, MSH6 and PMS2 genes.

## Which tumour finding points to Lynch syndrome?

Microsatellite instability or loss of an MMR protein on immunohistochemistry.

## If a tumour has lost MLH1 and its promoter is methylated, what does that suggest?

A sporadic cancer from epigenetic silencing of MLH1, not inherited Lynch syndrome.

## What is the second most common cancer in women with Lynch syndrome?

Endometrial cancer, whose risk can match or exceed that of colorectal cancer.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/lynch-syndrome/)

## Related conditions

- [Colorectal cancer](https://durgical.com/en/conditions/colorectal-cancer/)
- [Endometrial cancer](https://durgical.com/en/conditions/endometrial-cancer/)
- [Ovarian cancer](https://durgical.com/en/conditions/ovarian-cancer/)
- [Gastric cancer](https://durgical.com/en/conditions/gastric-cancer/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Lynch syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/lynch-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [MLH1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mlh1/) (MedlinePlus, US National Library of Medicine, 2026); [MSH2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/msh2/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Source: https://durgical.com/en/conditions/lynch-syndrome/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/lynch-syndrome/