Also Known As
Hereditary Nonpolyposis Colorectal Cancer
HNPCC
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This article waslast modified on June 12, 2020.
What is Lynch Syndrome?

Lynch syndrome is an inherited condition that can increase your risk of developing colon cancer, endometrial (uterine) cancer, and several other cancers. It is caused by a harmful genetic variant (pathogenic variant or likely pathogenic variants) of a mismatch repair gene.

Normally, the mismatch repair system fixes DNA errors. These errors commonly occur when DNA is copied as cells grow and divide. With Lynch syndrome, there is a change in one of the repair genes that prevents the mismatch repair system from working properly. The system is not able to fix DNA errors, which then start to accumulate. Eventually, the cells with these accumulated DNA errors can begin to grow and divide uncontrollably, which may lead to cancer.

The mismatch repair genes associated with Lynch syndrome include:

  • MLH1
  • MSH2
  • MSH6
  • PMS2
  • EPCAM

Lynch syndrome is the most common cause of inherited colon cancer and is also an important cause of endometrial cancer.

  • Colon cancer
    • Lynch syndrome is thought to be responsible for about 3% to 5% of all cases.
    • According to the Centers for Disease Control and Prevention (CDC), Lynch syndrome causes about 4,000 colorectal cancers each year.
    • Depending on the gene variant, Lynch syndrome is associated with a 20% to 80% lifetime risk of colon cancer (the average population risk is about 4% to 5%).
  • Endometrial cancer
    • Lynch syndrome is thought to be responsible for about 2% to 3% of all cases.
    • About 1,800 endometrial cancers are attributed to Lynch syndrome per year, according to the CDC.
    • Lynch syndrome is associated with a 15% to 60% lifetime risk of endometrial cancer (the average population risk is about 3%).

Lynch syndrome also increases the lifetime risk of other types of cancers, such as:

Accordion Title
About Lynch Syndrome
  • Who is more likely to have Lynch syndrome?

    The likelihood of having Lynch syndrome depends on a person's own medical history and their family history. You are more likely to have Lynch syndrome if you:

    • Are diagnosed with a cancer associated with Lynch syndrome, especially if diagnosed at a younger age (i.e., under age 50)
    • Have multiple biological relatives on the same side of the family that have been diagnosed with cancers associated with Lynch syndrome, especially colon cancer and/or endometrial cancer

    Normally, everyone inherits two copies of a gene—one from their mother and one from their father. Unlike some genetic conditions where both copies of the gene must have a pathogenic (disease-causing) variant, with Lynch syndrome, only one copy of a gene with a variant associated with Lynch syndrome is needed to cause an increased risk of cancer. This is called autosomal dominant inheritance. If you have Lynch syndrome, you have a 50% chance of passing the pathogenic gene variant on to each of your children.

    If you have increased likelihood of Lynch syndrome, your healthcare practitioner will talk to you about testing for Lynch syndrome.

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    (For more in-depth information on inheritance, read The Universe of Genetic Testing article.)

  • Signs and Symptoms

    Lynch syndrome itself does not result in symptoms, but if you have Lynch syndrome and develop a cancer, you may experience signs and symptoms of that cancer. (For details, see the links to specific cancer articles in the Related Content section).

    There may be signs in your personal or family medical history that lead your healthcare practitioner to suspect you have Lynch syndrome. People with Lynch syndrome may have a personal or strong family history of:

    • Colon cancer at a younger age (especially younger than age 50)
    • Multiple colon cancers at the same time
    • Additional colon cancers after treatment of an initial cancer
    • Other cancers, such as cancer of the:
      • Endometrium (lining of the uterus)
      • Liver or bile ducts
      • Brain
      • Kidneys
      • Ovaries
      • Pancreas
      • Stomach
      • Urinary tract

    (For more information on various types of cancers, see the links in the Related Content section.)

  • Testing

    Testing may be done to help determine whether you have increased likelihood of Lynch syndrome and, if so, to diagnose Lynch syndrome. If you are diagnosed with Lynch syndrome, testing may be done to screen for Lynch syndrome-related cancers so they can be found early, when they are most treatable.

    The testing approach typically depends on whether or not you already have or had a Lynch syndrome-related cancer and may involve the following:

    Tumor testing
    If you have colon cancer or sometimes another Lynch syndrome-related cancer and a tumor sample is available, then testing may first be done on the tumor sample (biopsy or surgical resection). Recent guidelines by multiple health organizations support testing all colorectal tumors for mismatch repair deficiency or microsatellite instability to see if those cancers are associated with Lynch syndrome.

    • Mismatch repair (MMR) protein testing (by immunohistochemistry) – normally, mismatch repair genes provide the instructions (coding) for making proteins that repair DNA errors. This test looks for these mismatch repair proteins in tumor tissue. A deficiency in one of these proteins may indicate that a mismatch repair gene is not functioning properly.
    • Microsatellite Instability (MSI) – this is genetic testing that looks for repeated sections of DNA that develop changes in length when there is a DNA mismatch repair problem. About 90% of people with colon cancer associated with Lynch syndrome have microsatellite instability-high (MSI-H) tumor testing. However, there are other reasons that your tumor might be MSI-H (see below). Only about 10% to 30% of people with microsatellite instability-high tumor testing have Lynch syndrome.
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      variants in the mismatch repair genes.

    These tumor tests can't diagnose Lynch syndrome, but they can help determine whether you should consider genetic testing for Lynch syndrome (see below). Tumor testing can sometimes indicate the probable gene involved.

    Genetic testing
    You may consider genetic testing if you have increased likelihood of having Lynch syndrome. This may be based on:

    • Your tumor test results if you've had a Lynch-syndrome related cancer
    • Your medical history and/or family history

    Prior to genetic testing for Lynch syndrome, it is typically recommended that you have genetic counseling to evaluate whether you have increased likelihood of the condition.

    There are screening tools to help determine whether you are likely to have Lynch syndrome and therefore may benefit from genetic testing. Criteria have been established to help identify patients who may have Lynch syndrome. Two guidelines are commonly used:

    Amsterdam II Criteria—genetic testing is recommended if you fit all of these criteria:

    1. Three or more relatives with Lynch syndrome-associated cancer, one of whom is a first-degree relative (e.g., mother, father, sibling) of the other two
    2. Cancer involving at least two generations in your family
    3. One or more of the related cancers diagnosed in a relative before 50 years of age

    Revised Bethesda Guidelines—genetic testing is recommended if you fit any one of these criteria:

    1. Diagnosis of colorectal cancer or endometrial cancer when you are younger than 50 years of age
    2. More than one colon cancer at the same time (synchronous), additional colon cancers at another time (metachronous), or other Lynch syndrome-associated tumors, regardless of how old you are
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    4. Diagnosis of colorectal cancer in one or more first-degree relatives with a Lynch syndrome-related tumor, with one of the diagnoses before 50 years of age
    5. Diagnosis of colorectal cancer in two or more first-degree (parents, siblings, children) or second-degree relatives (uncles, aunts, nieces, nephews, or grandparents) with Lynch syndrome-related cancers, at any age 

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    Genetic testing approaches:

    • If you have a Lynch syndrome-related cancer, the results of the tumor tissue tests can help guide genetic testing. If tumor testing results indicate the probable gene involved, then the test for that gene alone may be performed. If the tissue results are not available, or do not fit the patterns described above, but Lynch syndrome is still suspected, then more comprehensive testing may be performed, such as a Lynch syndrome gene panel.
    • If Lynch syndrome has been genetically diagnosed in a family member, then targeted testing for the familial pathogenic gene variant may be performed.

    See the article Lynch Syndrome Genetic Testing for more details on genetic testing, including:

    • Multi-gene panel testing
    • Single gene sequencing with deletion and duplication analysis
    • Targeted testing for known familial variants

    Other tests
    Besides tumor testing and genetic testing for Lynch syndrome, additional testing may be performed to help diagnose, stage, and monitor your cancer. (For more details, see the Related Content section for links to articles on specific types of cancer.)

    Screening tests for cancers associated with Lynch syndrome
    If you have Lynch syndrome, there are some tests that can be done to screen for related cancers so they may be detected early, when they are most treatable. Talk to your healthcare practitioner about these tests and other steps you can take to prevent cancer and/or lower your risk of cancer.

    Screening for colon cancer:
    The American Cancer Society (ACS) says that if your family is known to carry a Lynch syndrome gene variant, then:

    • Family members who have tested positive for a pathogenic variant in one of the Lynch syndrome genes, and any family member who has not been tested, should start colonoscopy screening in their early 20s. It should start 2 to 5 years sooner than the youngest age that a family member has been diagnosed with a Lynch syndrome-related cancer. The colonoscopy should be repeated every 1 to 2 years.
    • Family members who have tested negative for the familial pathogenic variant are not at an increased risk for developing cancer and thus can follow the usual guidelines for colon cancer screening.

    Other types of colon cancer screening, such as stool DNA or fecal occult blood tests are not recommended for people who may be at an increased risk for colon cancer.

    Other lab tests and imaging scans may be done on a regular basis to screen for various cancers if you have Lynch syndrome. Examples include:

    • Endometrial cancer: Transvaginal ultrasound and endometrial biopsy every 1 to 2 years, beginning between age 30 and 35 years
    • Ovarian cancer: CA-125 blood test and/or transvaginal ultrasound every year
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      Urinalysis every year starting between age 30 and 35 years
    • Stomach and other digestive tract cancer: Upper endoscopies every 3 to 5 years starting between age 30 and 35 years
  • Prevention and Treatment

    Prevention and treatment depend on your situation and whether or not you have or had cancer. Your healthcare practitioner will discuss your options with you.

    If you have cancer, your treatment will depend on the type and stage. See the Related Content section for links to cancer-specific articles and other resources with additional details on treatments.

    Colon cancer:

    • Treatments may include chemotherapy, targeted therapy, or immunotherapy. For more on this see the article on Colon Cancer.
    • When you have been diagnosed with Lynch syndrome and have colon cancer, it is typical to remove most of your colon to minimize cancer recurrence.
    • Most of the colon may also be removed as a preventive measure in some cases when you carry a Lynch syndrome gene variant.

    Other cancers

    • Some women may choose to have their uterus and ovaries removed to prevent endometrial cancer and ovarian cancer, typically after childbearing years.
    • Some studies suggest that taking aspirin each day helps to lower the risk of cancers associated with Lynch syndrome. However, more research is needed to confirm this.
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