- Clinical science
Lynch syndrome, or hereditary nonpolyposis colon cancer (HNPCC), is a familial cancer syndrome caused by an autosomal dominant mutation in DNA mismatch repair (MMR) genes. Patients develop a small number of adenomas that can rapidly progress to colorectal cancer (CRC), resulting in a considerably earlier presentation compared to that of sporadic colorectal cancer. Individuals with Lynch syndrome are also at an increased risk of developing other forms of cancer, especially endometrial, gastric, and ovarian cancer. The patients are asymptomatic until presenting with symptoms of advanced cancer. To identify individuals at high risk for Lynch syndrome, patients are assessed according to the Amsterdam II criteria. Subsequent genetic analysis with detection of MMR mutations confirms the diagnosis. Treatment consists of surgical colectomy and chemotherapy. Surgery may also be preventative and is recommended in addition to routine screenings for colorectal cancer and the associated tumors.
- Most common cause of inherited CRC
- Increased lifetime risk of associated cancers (by age 70)
Epidemiological data refers to the US, unless otherwise specified.
A suspected diagnosis is based on a positive family history according to the Amsterdam II criteria. Genetic testing confirms the diagnosis.
The Amsterdam II criteria are used to identify individuals who are likely to be mutation carriers for Lynch syndrome.
|Amsterdam II criteria|
Presence of at least three relatives with a Lynch syndrome-associated cancer; all the following criteria should be present:
3-2-1 rule: (3 affected family members, 2 generations, 1 relative under 50 years of age).
|Revised Bethesda guidelines|
Individuals should be tested for MSI in the following situations:
First test: immunohistochemistry (IHC) testing
- Detection of microsatellite instabilities in tumor tissue
- No evidence of MSI rules out Lynch syndrome
- Confirmatory test: germline testing via DNA sequencing
- For diagnosis of CRC see
Surgery (most commonly one of the following procedures)
- Subtotal colectomy with ileorectal anastomosis
- Total colectomy with ileostomy
- Total colectomy with ileorectal anastomosis
- For more specific guidelines regarding management, see
- For women with Lynch syndrome, prophylactic hysterectomy and bilateral salpingo-oophorectomy should be offered at the end of child-bearing age.
- Genetic testing is generally not recommended for at-risk individuals < 18 years of age
- It is recommended to start genetic screening 10 years before the earliest manifestation of the condition in the family
Cancer screening: for Lynch syndrome patients with a confirmed mutation or that meet Amsterdam or Bethesda criteria
- Annual colonoscopy: starting 2–5 years before the earliest case of a tumor in the family
- Annual pelvic examination with transvaginal sonography and endometrial biopsy starting at 30–35 years of age or 3–5 years before the earliest case of a tumor in the family
- Annual upper endoscopy with biopsy of the gastric antrum starting at 30–35 years of age
- Annual physical exam and urinalysis
- Total colectomy: considered the only method of preventing CRC; not generally recommended