Hereditary Colon Cancer - Lynch Syndrome

About 3% to 5% of colorectal cancers are believed to be caused by mutations in the MLH1MSH2MSH6PMS2, or EPCAM genes 40. When someone carries a mutation in any of these genes, they have a condition called Lynch syndrome. Lynch syndrome is also called Hereditary Non-polyposis Colorectal Cancer syndrome (HNPCC).

Myriad offers testing to determine whether a patient is a carrier of any one of these gene mutations.  When assessing the risk of carrying these mutations a patient’s personal and family history is collected to investigate the risk for Lynch syndrome. Once a patient is identified as being at increased risk for Lynch syndrome, genetic test results provide the most accurate means of cancer risk assessment for a patient.

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

  • Colorectal cancer
  • Endometrial (uterine) cancer
  • Ovarian cancer
  • Stomach cancer
  • And, rarely, urinary/renal, pelvis, biliary tract, small bowel, pancreas, and brain cancers
  • Some patients may also develop sebaceous adenomas, a non-cancerous tumor of an oil-producing gland

Colaris Increase Graph


Hereditary Cancer Testing for Colon Cancer

The following questions can be asked to help determine whether someone has a higher risk for colon cancer because of their own cancer history and their family's history.

Knowing the potential risk can help the healthcare provider and patient make better, more informed decisions about the patient’s health, before the onset of cancer or before a second cancer has a chance to develop. Testing should be considered for hereditary colon cancer if:

The Patient:

  • Has had colorectal or endometrial cancer before age 50
  • Has had 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 2 or more Lynch syndrome cancers** at any age
  • Has had a Lynch syndrome cancer** with 1 or more relatives with a Lynch syndrome cancer**
  • Has a previously identified Lynch syndrome mutation in the family

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

**Lynch-associated cancers include colon, endometrial, gastric, ovarian, ureter/renal pelvis, biliary tract, small bowel, pancreas, brain and sebaceous adenomas.

*Assessment criteria based on medical society guidelines.  For these individual medical society guidelines, go to www.myriadpro.com/guidelines

To help assess whether someone is a candidate for testing, they can take the Hereditary Cancer Quiz. This quiz can help them get the information they need to discuss with their risk of cancer with their healthcare provider and ask for further evaluation. If someone matches any of the red flags above or takes the quiz and finds red flags in their own history or their family history, they may benefit from hereditary cancer testing.


Hereditary Colon Cancer - Polyposis Syndrome

Approximately 2% of all colon cancer is thought to be caused by an adenomatous polyposis condition.81,82 They can be categorized into three conditions:

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

Classic familial adenomatous polyposis (FAP) and attentuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene.  MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene.  Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as "biallelic MYH mutations").  Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected).83  The MYH 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.

When assessing hereditary cancer risk, a patient's personal and family history is collected to investigate the risk for a polyposis syndrome.  Once a patient is identified as being at increased risk for one of these syndromes, genetic test results provide the most accurate means of cancer risk assessment for a patient.  It is important to note that approximately 20% to 30% of FAP cases are caused by new mutations, meaning that an APC germline mutations may be present in an individual even if it is absent in both parents.84  Also, due to the autosomal recessive inheritance pattern of MAP, many affected patients have no relatives with colorectal polyps or cancer.83 Genetic testing is the only way to identify truly at-risk family members.

Finding patients at risk for adenomatous polyposis syndromes and following up with them is perhaps the most critical step in changing hereditary cancer outcomes.  The following red flags* in a patient's personal or family history indicate an increased risk for a germline mutation in APC or MYH and help determine appropriate candidates for testing:

  • Individuals clinically affected with FAP (100 or more colorectal adenomas)
  • Individuals with multiple colorectal adenomas (usually 10 or more cumulative adenomas)
  • Relatives of APC or MYH mutation carriers

*Assessment criteria based on medical society guidelines.  For these individual medical society guidelines, go to www.myriadpro.com/guidelines


Colaris

About COLARIS®

COLARIS® testing assesses a person’s risk of developing hereditary colorectal cancer and a woman’s risk of developing hereditary uterine cancer. COLARISPLUS detects disease-causing mutations in the MLH1, MSH2, MSH6, PMS2, EPCAM, and MYH genes which are responsible for the majority of Lynch syndrome and MYH-associated polyposis (MAP) cases.

COLARIS Results

The results of COLARIS testing help healthcare providers and their patients make more informed healthcare decisions.  For example:

  • A patient who knows they carry a mutation associated with Lynch syndrome can start cancer screening at an earlier age. They can also choose options like risk-reducing medications and preventive surgery
  • Healthcare providers can help patients move forward with the right action plan for their particular risks
  • Patients already diagnosed with cancer may be able to prevent a second cancer
  • Test results can help relatives learn and understand more about inherited risk and how it may affect them

Colaris logo

About COLARISAP®

COLARISAP® testing assesses a person’s risk of developing hereditary colorectal polyps and cancer. COLARISAPPLUS detects mutations in the APC and MYH genes, which cause adenomatous polyposis colon cancer syndromes, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and MYH -associated polyposis (MAP).

COLARISAP Results

The results of COLARISAP testing help healthcare providers and their patients make more informed healthcare decisions.  For example:

  • A patient who knows they carry a mutation associated with a polyposis syndrome can start cancer screening at an earlier age. They can also choose options like risk-reducing medications and preventive surgery
  • Healthcare providers can help patients move forward with the right action plan for their particular risks
  • Patients already diagnosed with cancer may be able to prevent a second cancer
  • Test results can help relatives learn and understand more about inherited risk and how it may affect them

Personalized Medicine for Colon Cancer

About TheraGuide®

TheraGuide 5-FU testing assesses a person’s risk of developing a severe toxic reaction to 5-FU-based chemotherapy. It detects variations in 2 genes, dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthetase (TYMS) that are responsible for a significant portion of serious adverse reactions to 5-FU-based therapy.