Hereditary nonpolyposis colorectal cancer screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

According to the Bethesda guidelines and Amsterdam criteria, screening for hereditary nonpolyposis colorectal cancer by genetic testing is recommended among patients with family history or/and a confirmed diagnosis of colorectal cancer under age 50 years.

• According to the Bethesda guidelines and Amsterdam criteria, screening for hereditary nonpolyposis colorectal cancer by genetic testing is recommended among patients with family history or/and a confirmed diagnosis of colorectal cancer under age 50 years.^[1][2]
• The Amsterdam and Bethesda guidelines are useful for identifying cancer patients who are most likely to be hereditary nonpolyposis colorectal carriers as ideal candidates for genetic testing.
• Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming.
• Microsatellite instability can be observed in the majority of patients with colorectal cancer.
• Immunohistochemistry and microsatellite instability profiling strategy is the most advanced way of identifying candidates for genetic testing for the hereditary nonpolyposis colorectal cancer.
• The Amsterdam Criteria I and II identify patients for colonoscopic screening and approximately 40 – 80% of the patients meet these criteria.
• The revised Bethesda criteria are used to identify patients for molecular screening of hereditary nonpolyposis colorectal cancer.
• Approximately 80% of patients are identified using the Bethesda criteria, although the specificity is low.^[3][4]

The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:^[1]

Amsterdam Criteria I:

• Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, or sibling) relative of the other two
• Two successive affected generations
• One or more colon cancers diagnosed under age 50 years
• Familial adenomatous polyposis (FAP) has been excluded

Amsterdam Criteria II:

• Three or more family members with HNPCC-related cancers, one of whom is a first degree relative of the other two
• Two successive affected generations
• One or more of the HNPCC-related cancers diagnosed under age 50 years
• Familial adenomatous polyposis (FAP) has been excluded

The revised Bethesda Guidelines are designed for identifying individuals at risk for hereditary nonpolyposis colorectal cancer, and therefore recommend microsatellite instability testing.^[5]

Revised Bethesda guidelines:

• Colorectal cancer diagnosed in a patient aged < 50 years

• Presence of synchronous, metachronous colorectal or other Lynch syndrome‐related tumors, regardless of age

• With MSI‐H phenotype diagnosed in a patient aged < 60 years

• Patient with colorectal cancer and a first‐degree relative with a Lynch syndrome‐related tumor, with one of the cancers diagnosed at age < 50 years

• Patient with colorectal cancer with two or more first‐degree or second‐degree relatives with a Lynch syndrome‐related tumor, regardless of age

• Lynch syndrome‐related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter, renal pelvis, biliary tract and brain tumors, sebaceous gland adenomas and keratoacanthomas, and carcinoma of the small bowel

• According to Netherlands Surveillance Protocol for Carriers of an MMR-gene mutation, there is sufficient evidence to recommend routine screening for HNPCC-related cancers.^[6][7]

• Recommended annual screening for patients with hereditary nonpolyposis colorectal cancer (age 25 onwards or beginning no later than 5 years before the lowest age of onset in family) should include:^[7]

• Physical examination
• Abdominal ultrasound
• Colonoscopy
• Upper gastrointestinal endoscopy (age 35 onwards)
• Gynecological examination including transvaginal ultrasound
• Endometrial pipelle biopsy (age 35 onwards)
• Skin surveillance
• Urinalysis

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