This document addresses genetic testing for the following types of hereditary colorectal cancer:

• Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer);
• Familial Adenomatous Polyposis (FAP);
• Attenuated FAP (AFAP); and
• MYH-associated Polyposis (MAP).

This document does not address panel testing for colorectal cancer susceptibility. Please refer to:

• GENE.00052 Whole Genome Sequencing, Whole Exome Sequencing, Gene Panels, and Molecular Profiling

For additional information on genetic testing for malignant conditions, please refer to:

• CG-GENE-14 Gene Mutation Testing for Cancer Susceptibility and Management
• CG-GENE-16 BRCA Genetic Testing

Note: Although immunohistochemistry (IHC) and microsatellite instability (MSI) are discussed in this document, this document is not meant to provide testing criteria for IHC or MSI.

Clinical Indications

Medically Necessary:

Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer [HNPCC])

1. Genetic testing for Lynch syndrome is considered medically necessary when information is available that may guide targeted testing, (that is: one of criteria A or B) and all of criteria C are met:
   1. IHC shows loss of nuclear staining for one or more of the mismatch repair enzymes and gene testing is guided by these results; or
   2. The individual has a family history of a known mutation in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes; and
   3. Genetic counseling, which encompasses all of the following components, has been performed:
      1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
      2. Education about inheritance, genetic testing, disease management, prevention and resources; and
      3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
      4. Counseling for the psychological aspects of genetic testing.
2. Genetic testing for Lynch syndrome is considered medically necessary when information that may guide targeted testing is unavailable, (that is: one of criteria A), and any one of criteria B through K and all of criteria L are met:
   1. Information that may guide targeted testing is unavailable:
      1. There are no IHC tumor testing results; or
      2. There is no family history of a known mutation in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes; or
      3. The affected family member or proband is unavailable for testing; and
   2. Individual has a colorectal or endometrial cancer diagnosed prior to 50 years of age; or
   3. Individual with colorectal or endometrial cancer diagnosed at any age when there is a family history of a first-degree or second-degree relative with Lynch syndrome-related cancer^§ diagnosed prior to 50 years of age; or
   4. Individual with colorectal or endometrial cancer diagnosed at any age when there is a family history of 2 or more first-degree or second-degree relatives with Lynch syndrome-related cancer^§ diagnosed at any age; or
   5. The individual has a history of synchronous or metachronous Lynch syndrome-related tumor(s) ^§, regardless of age; or 
   6. The individual has a personal history of colorectal or endometrial cancer and the tumor shows evidence of mismatch repair deficiency (either high microsatellite instability [MSI] or loss of mismatch repair protein expression) at any age; or
   7. Individual has a predicted risk for Lynch syndrome greater than 5% on one of the following prediction models: MMRpro, PREMM or MMRpredict; or   
   8. The individual for whom the test is requested, has a first-degree relative with 2 or more Lynch syndrome-related tumors^§, including synchronous and metachronous tumors; or
   9. The individual for whom the test is requested, has 2 or more first- or second-degree relatives with a history of a Lynch syndrome-related cancer^§, including at least 1 relative which was diagnosed with a Lynch syndrome-related cancer^§ prior to age 50; or
   10. The individual for whom the test is requested, has a first-degree relative with colorectal cancer or endometrial cancer diagnosed prior to age 50; or
   11. The individual for whom the test is requested, has a family history of 3 or more first-degree or second-degree relatives with Lynch syndrome-related cancers^§, regardless of age; and
   12. Genetic counseling, which encompasses all of the following components, has been performed: 
       1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
       2. Education about inheritance, genetic testing, disease management, prevention and resources; and
       3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
       4. Counseling for the psychological aspects of genetic testing.
          ​​​​§ Lynch-related tumors (cancers) include: colorectal, gastric, small bowel, endometrial, ovarian, pancreas, ureter, renal pelvis, biliary tract, brain, sebaceous gland adenomas and keratocanthomas.

Familial Adenomatous Polyposis (FAP) and Attenuated FAP (AFAP)

1. Genetic testing to detect mutations in the APC (adenomatous polyposis coli) gene is considered medically necessary when any one of criteria A through D and all of criteria E are met:
   1. Individuals with greater than 10 adenomatous colonic polyps during their lifetime; or
   2. First- or second-degree relatives of individuals diagnosed with FAP or AFAP; or
   3. First- or second-degree relatives of individuals with a known APC gene mutation; or
   4. Individuals with a personal history of a desmoid tumor; and
   5. Genetic counseling, which encompasses all of the following components, has been performed:
      1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
      2. Education about inheritance, genetic testing, disease management, prevention and resources; and
      3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
      4. Counseling for the psychological aspects of genetic testing.

MYH (Human MutY homolog)-associated Polyposis (MAP)

1. Genetic testing for MYH (also known as MUTYH) -associated polyposis (MAP) is considered medically necessary when either criterion A or B and all of criteria C are met:
   1. The individual has greater than 10 adenomatous colonic polyps; or
   2. The individual is asymptomatic and has a first-degree relative with known MAP mutation; and
   3. Genetic counseling, which encompasses all of the following components, has been performed:
      1. Interpretation of family and medical histories to assess the probability of disease occurrence or recurrence; and
      2. Education about inheritance, genetic testing, disease management, prevention and resources; and
      3. Counseling to promote informed choices and adaptation to the risk or presence of a genetic condition; and
      4. Counseling for the psychological aspects of genetic testing.

Not Medically Necessary:

Genetic testing for HNPCC, FAP, AFAP or MAP is considered not medically necessary in individuals not meeting any of the criteria above.