Lynch syndrome

Epidemiology

Prevalence
- Most common cause of inherited CRC
Increased lifetime risk of associated cancers (by age 70)
- Endometrial cancer: up to 40%
- Gastric cancer: ∼ 10%
- Ovarian tumors: ∼ 10%
- Urothelial cancer: up to 10%
- Skin: ∼ 4%

Etiology

Hereditary disease: autosomal dominant with varying penetrance
Mutations in various DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) cause microsatellite instability.
- Increased occurrence of adenomas with ∼ 80% risk of progression to carcinomas
See Hereditary cancer syndromes

Pathophysiology

Clinical features

Patients are usually asymptomatic until CRC develops.
Turcot syndrome: presence of Lynch syndrome-related CRC and brain tumors (especially gliomas)

Diagnostics

Mnemonic

3-2-1 rule: (3 affected family members, 2 generations, 1 relative under 50 years of age).

Amsterdam II criteria
- Presence of at least three relatives with a Lynch syndrome-associated cancer; all the following criteria should be present:
  - One should be a first-degree relative of the other two
  - At least two consecutive generations affected
  - At least one relative with a diagnosis before 50 years of age
  - Exclude cases of familial adenomatous polyposis.
  - Verify tumors with pathological examination.

Treatment