Information for Health Professionals, Information for Patients, Lynch Syndrome, Screening Guidelines

EGAPP™ Recommendation Statement: Genetic testing for Lynch Syndrome


EGAPP™ Recommendation Statement

EGAPP™ Recommendation Statement Adobe PDF file [PDF 219 KB]External Web Site Icon

“The Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group found sufficient evidence to recommend offering genetic testing for Lynch syndrome to individuals with newly diagnosed colorectal cancer (CRC) to reduce morbidity and mortality in relatives. We found insufficient evidence to recommend a specific genetic testing strategy among the several examined.”

Summary of Findings on Genetic Testing for Lynch Syndrome for the General Public

General Public:
Genetic Testing for Lynch Syndrome

In 2009, the independent, non-federal Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working GroupExternal Web Site Icon reviewed the scientific evidence for genetic testing for Lynch syndrome (hereditary colorectal cancer) and developed a recommendation statement about the appropriate use of this testing. This brief summary of the EGAPP™ recommendation statement can help the general public understand what is intended by the EGAPP™ recommendation and where to find more information.

This information may be helpful for people with a recent diagnosis of colorectal cancer (cancer of the colon or rectum) and their close family members.

  • What is the purpose of genetic testing for Lynch syndrome for people newly diagnosed with colorectal cancer?

    Genetic testing is used to find out if a person’s colorectal cancer is hereditary (caused by an inherited gene change), so that family members can learn if they are also at increased risk.  This could help to protect them from getting this disease.

  • What is Lynch syndrome?

    About 3% of colorectal cancer cases are due to an inherited condition known as Lynch syndrome (sometimes referred to as hereditary nonpolyposis colorectal cancer or HNPCC).  People with this condition have a greatly increased chance to develop colorectal cancer, especially at a young age (younger than 50 years).  Children, sisters, and brothers of people with Lynch syndrome have a 50% chance to inherit the condition. Parents and other blood relatives such as grandparents, aunts, uncles, nieces and nephews are also at increased risk to have Lynch syndrome.

  • Who developed this recommendation?

    The EGAPP™ Working Group is a group of scientists and health care experts who review available research and evidence to make recommendations about the use of genetic tests.  This independent, non-government body includes representatives from universities, industry, clinical practice, insurance companies, and public health.

  • Did EGAPP™ recommend the use of genetic testing for newly diagnosed colorectal cancer patients?
    • YES:  The EGAPP™ Working GroupExternal Web Site Iconfound good scientific evidence to show that if individuals with colorectal cancer are found to have Lynch syndrome by genetic testing, their family members can benefit by:
      • undergoing genetic testing to learn if they are also at increased genetic risk.
      • if positive for the gene change, having earlier and more frequent screening which can prevent colorectal cancer.
    • They concluded that all people with a new diagnosis of colorectal cancer should be offered counseling and educational materials about genetic testing for Lynch syndrome.

 

Other Information

  • Are there other people the test might help?
    Although the EGAPP recommendation did not address use of testing in other situations, 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 evaluation for Lynch syndrome.
  • How do I find out more about the condition/test?
    In addition to talking with your health care provider, the Web sites below provide additional information on colorectal cancer, Lynch syndrome, cancer genetic testing, and access to genetic counseling services.

    Health Professionals:
    More About the EGAPP™ Lynch Syndrome Recommendation

    This page contains more information about the EGAPP Lynch syndrome recommendation for health professionals.

    For more information about genetic testing for Lynch syndrome that is not part of the EGAPP recommendation, see More About Genetic Testing for Lynch Syndrome.

    EGAPP™ Evidence Review at a Glance

    Testing Approach Application Quality of Evidence
    Adequacy of information to address:
    Overall Recommendation*
    Analytic Validity Clinical Validity Clinical Utility
    DNA analysis of mismatch repair (MMR) genes: (MLH1, MSH2, MSH6, PMS2) Diagnostic Testing Adequate Convincing Adequate Sufficient evidence to recommend use for the benefit of relatives
    Microsatellite Instability (MSI) Preliminary (Screening) Test Convincing / Adequate
    Immunohisto-chemistry (IHC) Preliminary (Screening) Test Convincing / Adequate
    Methylation Status (BRAF V600E mutation) Preliminary (Screening) Test (Supplemental to IHC) Adequate

    *Overall recommendation was decided on the basis of a) evidence indicating moderate level of net health benefits to relatives, and b) contextual factors.


    EGAPP™ Recommendation Statement Adobe PDF file [PDF 219 KB]External Web Site Icon

    “The Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group found sufficient evidence to recommend offering genetic testing for Lynch syndrome to individuals with newly diagnosed colorectal cancer (CRC) to reduce morbidity and mortality in relatives. We found insufficient evidence to recommend a specific genetic testing strategy among the several examined.”

    Considerations for Practice

    Note: See Contextual Factors Identified by EGAPP™ for more information.

    • All patients with a new diagnosis of colorectal cancer (regardless of age or family history) should be offered counseling and educational materials regarding genetic testing for Lynch syndrome.
      • The primary benefit will be the identification of relatives who also carry a gene mutation for Lynch syndrome. Affected relatives can be offered appropriate screening beginning at age 20-25.
    • Colonoscopy every one to two years is recommended for these patients and their relatives who test positive for Lynch syndrome beginning at age 20-25 years. Although there is not enough research to indicate that colorectal cancer due to Lynch syndrome should be treated differently than non-Lynch related colorectal cancer, individuals with Lynch syndrome are at increased risk for additional cancers and second primary colon tumors.
    • Individuals with colorectal cancer should be offered genetic testing even if there are no other family members with Lynch syndrome cancers. This is because family history was found to be less useful as a first step than strategies involving tumor testing in identifying Lynch syndrome in individuals with colorectal cancer. However, family history may still be an important decision tool for identifying individuals in the general population for referral to genetic counseling services to evaluate risk for hereditary colorectal cancer.

    See More Considerations for Practice for additional information that is not part of the EGAPP™ recommendation.


    Testing Approaches

    Several testing approaches are potentially effective for identifying Lynch syndrome. DNA analysis has the highest sensitivity and specificity, but is also the most expensive. Most protocols directed at screening unselected colon cancers begin with preliminary testing of tumor tissue by MSI and/or IHC (with or without BRAF mutation).

    • Diagnostic testing: Typically performed on blood; identifies an inherited mutation in one of the Lynch syndrome genes.
      • DNA analysis (gene sequencing, deletion/duplication testing) for the mismatch repair (MMR) genes: MLH1, MSH2, MSH6, and PMS2.
    • Preliminary (Screening) Tests: Performed on tumor tissue; does not identify Lynch (MMR) gene mutations, but is used to guide subsequent diagnostic testing via DNA analysis.
      • MSI testing of tumor tissue: those with high instability either proceed to DNA analysis for MLH1, MSH2, MSH6, and PMS2 or to IHC testing.
      • IHC testing of tumor tissue: those with negative staining would proceed to DNA analysis of the gene/genes indicated.
      • Modification of Strategy 3, such that tumor tissue of patients with negative staining for MLH1 on IHC is tested for the BRAF V600E mutation to determine methylation status.  If the BRAF mutation is not found, the individual continues on for MLH1 DNA analysis.

    For more information about genetic testing approaches for Lynch syndrome, please see the National Library of Medicine, GeneReviews Web siteExternal Web Site Icon. (Note: This Web site does not necessarily reflect the opinions or recommendations of the Centers for Disease Control and Prevention or the EGAPP Working Group.)


    Contextual Factors Identified by EGAPP

    • Due to limited benefit to the colorectal cancer (CRC) patient, informed consent before microsatellite instability (MSI) or immunohistochemistry (IHC) testing is recommended.
    • There is no substantial evidence to show that identifying Lynch syndrome through routine genetic testing would lead to adverse psychological outcomes.
    • Evidence shows that there are relatively high levels of counseling and testing uptake among relatives and adherence to screening if patient is mutation positive.Top of Page

    Research Gaps Identified by EGAPP

    The EGAPP™ working group identified the need for research to address the following:

    • Better quality research regarding analytical validity of testing and laboratory proficiency testing;
    • Better quality studies evaluating clinical validity of various testing strategies;
    • Higher quality studies assessing clinical outcomes/clinical utility, effectiveness of screening;
    • Cost-effectiveness analyses to address testing strategies and impact on relatives
      (see More Considerations for Practice for additional information that is not part of the EGAPP™ recommendation);
    • Studies to assess whether the clinical care and screening of CRC patients with Lynch syndrome should be altered.

    For more information about genetic testing for Lynch syndrome that is not part of the EGAPP recommendation, see More About Genetic Testing for Lynch Syndrome.

 

About kjmonahan

Service lead for Family History of Bowel Cancer Clinic

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