Hereditary Nonpolyposis CRC

Families that meet the Amsterdam criteria have a clinical diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) (Table 94-2). Testing of an affected family member begins with germline analysis of MLH1 and MSH2; mutations in these genes account for 90% of mutations detected in this disorder. Starting with germline testing is often appropriate for individuals meeting one of the first three Bethesda criteria (Table 94-3). Approximately 60%

of Amsterdam-positive families will have a mutation in one of these two genes. If no mutation is found in MLH1 and MSH2, testing of MSH6 may be beneficial. No commercial testing for PMS1 or PMS2 exists. For individuals with HNPCC by clinical criteria or genetic analysis, annual colonoscopy begins at age 25 years, or 5 to 10 years before the earliest CRC diagnosis in the family, whichever is younger. Women should have annual transvaginal ultrasound with consideration of endometrial biopsy and/or serum CA-125. If a family HNPCC mutation is identified, any biological relatives who have this mutation should

TABLE 94-2. Amsterdam Criteria: Families That Meet All Criteria Have a Clinical Diagnosis of Hereditary Nonpolyposis Colorectal Cancer

Three relatives with colorectal cancer (one a first-degree relative of the other two) Two or more generations of colorectal cancer One or more cases of colorectal cancer diagnosed before age 50 years Familial adenomatous polyposis is excluded

TABLE 94-3. Bethesda Criteria: Individuals That Meet One or More Criteria are Suspicious for HNPCC

1. Individuals with cancer in families that fulfill the Amsterdam criteria

2. Individuals with two HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extracolonic cancers

3. Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or adenoma; one of the cancers diagnosed under age 45 years and the adenoma diagnosed under age 40 years

4. Individuals with colorectal cancer or endometrial cancer diagnosed under age 40 years

5. Individuals with right-sided colorectal cancer with an undifferentiated pattern (solid/cribiform) on histopathology diagnosed under age 45 years

6. Individuals with signet-ring cell-type colorectal cancer diagnosed under age 45 years

7. Individuals with adenomas diagnosed under age 40 years HNPCC = hereditary nonpolyposis colorectal cancer.

undergo surveillance as described above. Those relatives without the family mutation are unaffected and can follow general population screening guidelines. If genetic testing is inconclusive (no mutation is detected in an affected person or no affected person has undergone genetic testing), screening is based on family history.

Individuals that meet one or more of the Bethesda criteria are suspicious for HNPCC. Colorectal tumors from such individuals should be analyzed for microsatellite instability (MSI) at the five National Cancer Institute recommended marker sites. If the tumor is MSI-positive at two or more markers (MSI-High), germline testing of the individual is recommended, and screening intervals are determined as above. If the tumor is MSI-low or MSI-negative, HNPCC is less likely, and screening is based on family history.

Constipation Prescription

Constipation Prescription

Did you ever think feeling angry and irritable could be a symptom of constipation? A horrible fullness and pressing sharp pains against the bladders can’t help but affect your mood. Sometimes you just want everyone to leave you alone and sleep to escape the pain. It is virtually impossible to be constipated and keep a sunny disposition. Follow the steps in this guide to alleviate constipation and lead a happier healthy life.

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