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%

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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

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Pathophysiology

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Clinical features

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

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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.

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Treatment

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