Hereditary Colon Cancer

Who Should Be Tested for Lynch Syndrome

If a patient’s personal or family history indicates that he/she may be at an increased risk for Lynch syndrome, genetic test results provide the most accurate way to assess that patient’s cancer risk. Knowing the risk can help you and your patient make better and more informed decisions before the onset of cancer or before a second cancer has had a chance to develop.
Genetic testing for hereditary colon cancer should be considered if:*

The Patient:

• Has had colorectal or endometrial cancer before age 50
• Has had colorectal cancer with MSI-high histology before age 60
  • Mucinous
  • Signet ring
  • Tumor infiltrating lymphocytes
  • Crohn’s-like lymphocytic reaction histology
  • Medullary growth pattern
• Has had an abnormal MSI/IHC tumor test result (colorectal/endometrial)
• Has had two or more Lynch syndrome cancers^** at any age
• Has had a Lynch syndrome cancer and has one or more relatives with a Lynch syndrome cancer^**
• Has a previously identified Lynch syndrome mutation in the family
• Has a ≥5% risk of Lynch syndrome on one of the following mutation predication models: MMRpro, pREMM or MMR predict

The Patient’s Family:

• Has had two or more relatives with a Lynch syndrome cancer,^** one before the age of 50
• Has had three or more relatives with a Lynch syndrome cancer^** at any age
• Has a previously identified Lynch syndrome mutation in the family

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About Polyposis Syndrome

Approximately two percent of all colon cancer is thought to be caused by one of three adenomatous polyposis conditions:^2,3

• Familial adenomatous polyposis
• Attenuated familial adenomatous polyposis
• MYH-associated polyposis

Classic familial adenomatous polyposis (FAP) and attenuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene. Approximately 20 percent of APC-associated polyposis syndromes are caused by de novo mutations, in which an APC mutation is present in an individual, even though it is absent in both parents.⁴

MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene. This gene is an important part of the base excision repair (BER) pathway, which allows for repair of DNA mutations caused by oxidative damage to cells. Individuals with MAP have biallelic MYH mutations, or mutations in both of the MYH genes inherited from each parent. They often have no family history of colon cancer or polyps in their parents (although siblings may be affected).⁵

Since some polyposis syndromes like AFAP or MAP may not present with a significant personal/family history of colon cancer or colon polyps, genetic testing may be a useful tool to identify at risk individuals.^4,5 Myriad offers genetic testing to determine whether your patient is a carrier of any of the genetic mutations associated with Lynch syndrome.

Who Should Be Tested for a Polyposis Syndrome

Identifying people who are at risk for adenomatous polyposis syndromes and monitoring them is perhaps the most critical step in changing hereditary cancer outcomes. Genetic testing for a polyposis syndrome should be considered for:*

• Individuals with multiple colorectal adenomas (usually 10 or more cumulative adenomas)
• Personal history of a desmoid tumor, hepatoblastoma, cribriform-morular variant of papillary thyroid cancer
• Relatives of APC or MYH mutation carriers

You can use the Myriad Hereditary Cancer Quiz as a tool to help you identify patients who may benefit from hereditary cancer testing.

Using Hereditary Cancer Testing to Reduce Colon Cancer Risk and Improve Patient Care

In Lynch Syndrome

If hereditary cancer testing confirms the presence of a MLH1, MSH2, MSH6 or PMS2 mutation, the following medical management options may help reduce colon cancer risk and may either delay the onset of cancer or detect it at an earlier, more treatable stage: †

• Increased surveillance for colon, endometrial and ovarian cancer, including screening colonoscopy
• Surgical management
• Chemoprevention

In Polyposis Syndromes

If hereditary cancer testing confirms the presence of an APC or MYH mutation, the following medical management options may help reduce cancer risk and may either delay the onset of cancer or detect it at an earlier, more treatable stage:⁶

• Counseling for mutation carriers and their family members on the underlying cause of the cancer or adenomas.
• Increased surveillance and other interventions specifically for individuals with the APC or MYH gene mutations.
• Improved patient compliance through the use of tailored screening recommendations and preventive measures.
• Significantly improved outcomes and reduced medical costs through early diagnosis and treatment of cancer.

*Assessment criteria are based on individual medical society guidelines.

**Lynch-associated cancers include colon, endometrial, gastric, ovarian, urinary tract, renal/pelvic, biliary tract, small bowel, pancreatic, brain and sebaceous adenomas.

†Any discussion of medical management options is for general informational purposes only and does not constitute a recommendation. While genetic testing and medical society guidelines provide important and useful information, all medical management decisions should be made based on consultation between each patient and his or her healthcare professional.