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Cancer Genetics

Hereditary Non-polyposis Colorectal Cancer Screening Criteria



Is there some information regarding guidelines for testing and diagnosis of Hereditary Non-polyposis Colorectal Cancer(HNPCC) in the presence of only extra colonic cancers without any colorectal cancer?


Please bear with me in this; the answer is not entirely clear, and various geneticists and colorectal cancer specialists will disagree on various points.  The bottom line is, yes it is possible to suggest HNPCC without colon cancer, but one cannot not conclusively prove HNPCC, short of genetic testing.

The most commonly used and easiest criteria for diagnosis of HNPCC are the Amsterdam Criteria.  The Amsterdam Criteria were revised, and the revised criteria are known as the Amsterdam Criteria II, or the Modified Amsterdam Criteria.  They specify that:

1. The patient must be diagnosed with either colon cancer or one of the HNPCC-associated cancers, including endometrial, small bowel cancers or cancer of the renal pelvis.  Some practitioners also include bladder cancer and ovarian cancer in the spectrum of HNPCC associated cancers.  These last two cancers are found in HNPCC families, and are indeed part of the spectrum of cancers, but the ACII criteria did not include them.  Some feel that they should be considered as part of the spectrum in evaluating the family.

2. The family history must have three or more relatives with HNPCC associated cancers (see above for discussion), and one must be a first degree relative of the other two.  Example: patient with affected child and mother; patient with parent and uncle/aunt; patient with sibling and parent.

3. Colon cancer must involve at least two generations (only colon cancer? can HNPCC cancers substitute?  Not particularly clear.)

4. One or more of the colorectal cancers must be diagnosed before age 50. (What about the other cancers, even if colon cancer was diagnosed after age 50?)

Probably the most liberal interpretation would be that any of the HNPCC cancers could substitute for colon cancers in the above criteria.  The most conservative interpretation would rule against this.  In fact, a number of families with "atypical HNPCC" have been found to have mutations in one of the genes associated with HNPCC, MSH6.

Other criteria to consider are the Bethesda Criteria.  These criteria are to be used to determine who should have further evaluation for possible HNPCC.  This should include evaluation of tumor tissue for evidence of microsatellite instability and loss of expression of the mismatch repair proteins.

Briefly, people who should be evaluated further include those meeting any of the following criteria:

Individuals with two HNPCC associated cancers (see above) 

Individuals with colon cancer and a first degree relative with colon cancer or an HNPCC associated cancer and/or colon adenoma; with one of the cancers diagnosed before age 45 and the adenoma diagnosed before age 40

Individuals with colon cancer or endometrial cancer diagnosed before age 45 (what about other HNPCC associated cancers?)

Individuals with colon adenomas diagnosed before age 40.

With all that said, these are quite easy to fulfill, but meeting these criteria does not mean the patient has HNPCC, only that further evaluation is appropriate.  I fear I may have given you more than you ever wanted to know.  The best option is to request an appointment with a genetic counselor or a geneticist who specializes in hereditary cancers.  You can find a genetic counselor in your area by going to the website for the National Society of Genetic Counselors

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Response by:

Duane D Culler, PhD, MS Duane D Culler, PhD, MS
Clinical Instructor of Genetics
School of Medicine
Case Western Reserve University