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Key Features

  • Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant condition

  • Besides colorectal cancer, there is a markedly increased risk of other cancers, including cancers of

    • Endometrium

    • Ovary

    • Kidney or bladder

    • Hepatobiliary

    • Stomach

    • Small intestine

  • Accounts for up to 3% of all colorectal cancers

  • Caused by a defect in one of several genes

    • MLH1

    • MSH2

    • MSH6

    • PMS2

    • EPCAM, a promoter for MSH2

  • Associated with a 22–75% lifetime risk of colorectal carcinoma and a > 30% lifetime risk of endometrial cancer

  • Cancer develops at an earlier age (mean, 45–50 years) than sporadic nonhereditary cancers

  • Associated with markedly improved survival compared with sporadic colorectal cancers

Clinical Findings

  • Few colonic adenomas; adenomas flat, and more often contain villous features or high-grade dysplasia

  • Synchronous or metachronous cancers within 10 years occur in up to 45% of patients


  • Genetic evaluation is recommended for those with a personal or family history of colorectal cancer under age 50, a history of multiple family members with cancer, or a > 5% PREMM5 model-predicted chance of Lynch syndrome

  • Because personal and family history alone are insufficient to identify a significant proportion of patients with Lynch syndrome, the National Comprehensive Cancer Network recommends that all colorectal cancers should undergo testing for Lynch syndrome

  • Universal testing has the greatest sensitivity for the diagnosis of Lynch syndrome and is cost-effective

  • Individuals whose tumors have normal immunohistochemical staining or do not have microsatellite instability

    • Are unlikely to have germline mutations in mismatch repair genes

    • Do not require further genetic testing

    • Do not require intensive cancer surveillance

  • Germline testing for gene mutations is positive in > 90% of individuals whose cancers show absent histochemical staining of one of the mismatch repair genes or high level of microsatellite instability without a BRAF mutation


  • If genetic testing documents a Lynch syndrome gene mutation, then affected relatives should be screened with colonoscopy every 1–2 years

    • Begin at age 25 years or

    • Begin 5 years younger than the age of the family member in whom cancer was first diagnosed

  • Subtotal colectomy with ileorectal anastomosis if cancer is found (followed by annual surveillance of the rectal stump)

  • Endometrial aspiration or transvaginal ultrasound screening for endometrial cancer in women beginning at age 25–35 years

  • Consider prophylactic hysterectomy and oophorectomy in women at age 40 or once they have finished childbearing

  • Consider screening for gastric cancer with upper endoscopy every 2–3 years beginning at age 30–35 years

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