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Genetic Testing

Health Professionals:
More About Genetic Testing for Lynch Syndrome


This page contains general information about genetic testing for Lynch syndrome that is not part of the EGAPP recommendation but may be important for health professionals.

About Lynch Syndrome

Lynch syndrome refers to individuals with hereditary predisposition to colorectal cancer (CRC) and other malignancies as a result of an inherited mutation in a specific type of gene known as a mismatch repair (MMR) gene. Lynch syndrome includes those with an existing cancer as well as those who have not developed cancer. 

  • Also referred to as hereditary nonpolyposis colorectal cancer (HNPCC)
  • Autosomal dominant inheritance pattern (50% risk to offspring to inherit the gene mutation)
  • The lifetime risk for CRC in individuals with Lynch syndrome reported in the literature ranges from approximately 20-80%, dependent upon:
    • Gene involved
    • Sex of the individual
    • Population studied
  • Mean age of onset of  CRC is approximately 45 years
  • Increased risk for other malignancies including: endometrial, ovarian, urinary tract, gastric, small bowel, pancreatic, and sebaceous skin tumors
  • Further information on Lynch syndrome genetic and clinical characteristics:

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Public Health Implications

Public health practitioners may choose to use this information regarding Lynch syndrome to support public health activities in colorectal cancer screening programs, public health workforce development, and surveillance, such as:

  • Incorporating the EGAPP™ recommendation into existing public health programs focused on promoting colorectal cancer awareness and screening, including educational activities for consumers and providers.
  • Conducting workforce training to increase awareness of the importance of genetic testing for Lynch syndrome for individuals newly diagnosed with colorectal cancer according to the EGAPP™ recommendation.
  • Conducting workforce training to increase awareness of the importance of family history in evaluating risk for Lynch syndrome among healthy individuals in the general population.
  • Examining cancer registry data to determine the number of new diagnoses of colorectal cancer by location/facility in order to measure the potential impact of implementing genetic testing for Lynch syndrome for all newly diagnosed colorectal cancer patients.
  • Identifying those healthcare facilities with the existing infrastructure to implement genetic testing for Lynch syndrome for all newly diagnosed colorectal cancer patients.
  • Developing mechanisms to monitor rates of genetic testing (MSI, IHC, germline mutation analysis) being conducted on newly diagnosed colorectal cancer patients, perhaps in cancer registry systems.
  • Evaluating disparities in access to genetic testing and genetic counseling for Lynch syndrome.

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More Considerations for Practice

  • People with colorectal cancer diagnosed in the past (especially under age 50), and/or people with several family members with colorectal and/or uterine cancer may also benefit from genetic counseling and evaluation for Lynch syndrome testing (see Family History below for more information).
  • The Mallorca-group and the National Comprehensive Cancer Network also recommend increased surveillance for some non-colonic cancers associated with Lynch syndrome. 
  • Preliminary screening and diagnostic testing for Lynch syndrome is covered by some insurance companies, but not by all.
  • A detailed cost-effectiveness analysis* was completed after the EGAPP™ recommendation was published.  The four testing approaches evaluated were found to be cost effective in the following order, from most to least cost effective:
    • Preliminary screening of tumor tissue using IHC, plus BRAF
    • Preliminary screening of tumor tissue using IHC only
    • Preliminary screening of tumor tissue using MSI
    • Genetic sequencing (DNA analysis) for all 4 MMR genes

*The Cost-Effectiveness of Genetic Testing Strategies for Lynch Syndrome Among Newly Diagnosed Patients with Colorectal Cancer, published online on January 15, 2010 in Genetics in Medicine. Authors: Mvundura M, Grosse SD, Hampel H, Palomaki GE.

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Family History

Family history is important for identifying individuals without colorectal cancer in the general population who are at potential risk for Lynch syndrome.

  • Family history should include information on cancers in first (parents, siblings, children) and second-degree (grandparents, aunts/uncles, nieces/nephews, grandchildren) relatives on maternal and paternal sides, including cancer type and age of diagnosis.
  • Health care providers should consider referral for genetic counseling if family meets Amsterdam II or Revised Bethesda Criteria.

Amsterdam II Criteria: Gastroenterology 1999;116:1453–1456

  1. There should be at least three relatives with an HNPCC-associated cancer (CRC, cancer of the endometrium, small bowel, ureter, or renal pelvis)
  2. One should be a first-degree relative of the other two
  3. At least two successive generations should be affected
  4. At least one should be diagnosed before age 50
  5. Familial adenomatous polyposis should be excluded in the CRC case(s), if any
  6. Tumors should be verified by pathological examination

Revised Bethesda Guidelines: J Natl Cancer Inst 2004;96:261– 8; J. Med. Genet. 2007;44;353-362
Tumors from individuals should be tested for MSI in the following situations:

  1. CRC diagnosed in a patient who is less than 50 years of age.
  2. Presence of synchronous, metachronous colorectal, or other HNPCC associated tumors,* regardless of age.
  3. CRC with the MSI-H† histology‡ diagnosed in a patient who is less than 60 years of age.
  4. Patient with CRC and a first-degree relative with a Lynch syndrome-related tumour, with one of the cancers diagnosed at age < 50 years.
  5. Patient with CRC with two or more first-degree or second-degree relatives with a Lynch syndrome-related tumor, regardless of age.

*Hereditary nonpolyposis colorectal cancer (HNPCC)-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, and brain (usually glioblastoma as seen in Turcot syndrome) tumors, sebaceous gland adenomas and keratoacanthomas in Muir–Torre syndrome, and carcinoma of the small bowel.
†MSI-H = microsatellite instability–high in tumors refers to changes in two or more of the five National Cancer Institute-recommended panels of microsatellite markers.
‡Presence of tumor infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucinous/signet-ring differentiation, or medullary growth pattern.

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