Lynch syndrome is the most common cause of hereditary colon cancer. Myriad myRisk® Hereditary Cancer uses next-generation sequencing technology to identify patients who may be at risk so that they can take steps to lower their risk of cancer.

About Lynch Syndrome

About three to five percent of colorectal cancers are believed to be caused by mutations in the MLH1MSH2MSH6 , PMS2 or EPCAM genes.1  When a patient carries a mutation in any of these genes, he/she has a condition called Lynch syndrome also known as Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome .

People with Lynch syndrome are also at higher risk of developing several other types of cancer, including:

  • Endometrial cancer
  • Ovarian cancer
  • Gastric cancer
  • In addition, rarely, urinary tract, renal/pelvic, biliary tract, small bowel, pancreatic, and brain cancers

Some patients with Lynch syndrome may also develop sebaceous adenomas, noncancerous tumors of the sebaceous glands.

Myriad offers genetic testing to determine whether your patient is a carrier of any of the genetic mutations associated with Lynch syndrome.

risk of cancer in patients with lynch syndrome mutations

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

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

Get Your Custom Hereditary Cancer Quiz

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

medical management options for reducing colon cancer risk in lynch syndrome

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.

References

1. Giardiello FM, et al. Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2014 109:1159-79. PMID:25070057.

2. Burt R, Neklason DW. Genetic testing for inherited colon cancer. Gastroenterology 2005 May;128(6):1696-716.

3. Halford SE, et al. Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. Am J Pathol 2003;162(5):1545-8.

4. Jasperson KW, Burt RW. APC- Associated Polyposis Conditions. 2014 Mar 27. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK1345/ PMID: 20301519

5. Brand R, et al. MUTYH-Associated Polyposis. 2012 Oct 04. In: Pagon RA, et al., editors. GeneReviews® [Internet]. Available from http://www.ncbi.nlm.nih.gov/books/NBK107219/ PMID: 23035301

6. Provenzale D, et al. NCCN Clinical Practice Guidelines in Oncology® Genetic/Familial High-Risk Assessment: Colorectal. V 1.2015. May 4th. Available at http://www.nccn.org