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.

Lynch Syndrome

About three to five percent of colon or rectal cancers (colorectal cancers) are believed to be caused by mutations in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes.1 When someone carries a harmful mutation in any of these genes, they have a condition called Lynch syndrome, which is also called Hereditary Non-polyposis Colorectal Cancer (HNPCC) syndrome.

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

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

Some people with Lynch syndrome may also develop sebaceous adenomas, which are noncancerous tumors of an oil-producing gland in the skin.

risk of cancer in patients with lynch syndrome mutations

Assessing Your Risk for Lynch Syndrome

Myriad offers genetic testing to determine whether you are a carrier of any of the gene mutations associated with Lynch syndrome. In order to assess your risk of carrying these mutations, your healthcare professional may ask you questions about your personal and family medical history. If you are identified as being at an increased risk for Lynch syndrome, genetic testing provides the most accurate means of determining your risk of developing cancer.

To help you assess whether you may benefit from hereditary cancer genetic testing, take the Myriad Hereditary Cancer Quiz. This quiz can help you get the information you need to discuss your risk of cancer with your healthcare professional and ask for further evaluation.

Take the Hereditary Cancer Quiz

Risk Factors for Lynch Syndrome

Knowing your risk for Lynch syndrome can help you and your healthcare professional make better, more informed decisions about your health, before the onset of cancer or before a second cancer has had a chance to develop. Genetic testing for hereditary colon cancer with the Myriad myRisk® Hereditary Cancer test should be considered if:*

You have a personal history of:

  • Colorectal or endometrial cancer before age 50
  • Abnormal tumor test results (colorectal/endometrial)
  • Two or more Lynch syndrome cancers** at any age
  • A Lynch syndrome cancer** with one or more relatives also with a Lynch syndrome cancer**
  • A previously identified Lynch syndrome or MAP syndrome mutation in the family

You have any of the following family histories:

  • A first or second degree relative with colorectal or endometrial cancer before the age of 50
  • Two or more relatives with a Lynch syndrome cancer** before the age of 50
  • Three or more relatives with a Lynch syndrome cancer** at any age
  • A previously identified Lynch syndrome or MAP syndrome mutation in the family

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. It is important to note that approximately 20 percent of APC-associated polyposis syndromes are caused by new mutations, meaning that an APC mutation may be present in an individual, even if it is absent in both parents.4

MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene, which plays an important role in DNA repair. Individuals with MAP have mutations in both of their MYH genes, one from each parent, and 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 one of the gene mutations associated with a polyposis syndrome.

Assessing Your Risk for a Polyposis Syndrome

Myriad offers genetic testing to determine whether you are a carrier of a gene mutation associated with a polyposis syndrome. In order to assess your risk of carrying one of these mutations, your healthcare professional may ask you questions about your personal and family medical history. If you are identified as being at an increased risk for a polyposis syndrome, genetic testing may be a useful tool to determine your risk of developing cancer.

To help you assess whether you may benefit from hereditary cancer genetic testing, take the Myriad Hereditary Cancer Quiz. This quiz can help you get the information you need to discuss your risk of cancer with your healthcare professional and ask for further evaluation.

Risk Factors 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. In order to assess your risk of carrying a mutation in the APC or MYH genes, your healthcare professional may ask you questions about your personal and family medical history. Genetic testing for a polyposis syndrome should be considered if:

  • You have multiple colorectal adenomas (usually 10 or more cumulative adenomas)
  • You are a relative of an APC or MYH mutation carrier

Using Hereditary Cancer Testing to Reduce Your Colon Cancer Risk

In Lynch Syndrome

If the Myriad myRisk® Hereditary Cancer test confirms the presence of a MLH1, MSH2, MSH, PMS2 or EPCAM mutation, the following medical management options may help reduce cancer risk and may either delay the onset of cancer or detect cancer at an earlier, more treatable stage:

  • Increased surveillance for colon, endometrial (uterine) and ovarian cancer, such as starting cancer screening at an earlier age or being screened more frequently
  • Surgical management
  • Chemoprevention (risk-reducing medications)

In Polyposis Syndromes

If the Myriad myRisk® Hereditary Cancer test confirms the presence of an APC or MYH gene mutation, your healthcare professional may choose among the following medical management options to help reduce cancer risk and either delay the onset of cancer or detect it at an earlier, more treatable stage:

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

 

*Assessment criteria are based on medical society guidelines.

**Lynch syndrome-associated cancers include colon, endometrial (uterine), 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