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Lynch Syndrome

Lynch syndrome is an inherited condition that increases the risk of several types of cancer, including colorectal cancer and endometrial (uterine) cancer. Lynch syndrome is sometimes referred to as hereditary non-polyposis colorectal cancer (or HNPCC), though the two conditions are not exactly the same.

Key Facts

  • Lynch syndrome is one of the most common hereditary cancer syndromes. As many as three in every 100 people carry the gene mutation that causes it.
  • Lynch syndrome is inherited through an autosomal dominant pattern. This means that if one parent carries the gene mutation, their child has a 50 percent chance of carrying it.
  • A family history of colorectal or endometrial cancer is strongly linked to Lynch syndrome. Diagnosis can typically be confirmed through either tumor testing or genetic testing.
  • While Lynch syndrome itself has no cure, regular treatment options are available for any resulting cancer.

Causes

Lynch syndrome is caused by a genetic mutation in one of several types of genes involved in DNA mismatch repair. In normal cells, the DNA mismatch repair process helps correct any minor mistakes made as DNA is copied during cell division. But the genetic mutations associated with Lynch syndrome prevent cells from repairing these mistakes. This can lead to an accumulation of genetic damage and, eventually, cancerous growth.

The genes involved in Lynch syndrome are called:

  • MLH1
  • MSH2
  • MSH6
  • PMS2
  • EPCAM

A mutation in one of these genes is usually passed on from parents to children through an autosomal dominant pattern. This means that a child has a 50 percent chance of having Lynch syndrome if just one parent also has the mutation. More rarely, these mutations can also occur as a natural product of aging or through other causes that are still not completely understood. In these cases, they are called acquired mutations.

It is important to note that, although one’s risk increases with these mutations, not every person will necessarily develop cancer.

Symptoms

Lynch syndrome typically does not produce any symptoms until it has led to the development of cancer. In those cases, general cancer symptoms like weight loss and anemia may arise, as well as symptoms specific to the particular type of cancer. When Lynch syndrome leads to colorectal cancer, symptoms may include:

  • Bloody stool
  • Diarrhea
  • Constipation
  • Cramps and bloating

Diagnosis

The below set of criteria, called the Bethesda guidelines, help doctors diagnose Lynch syndrome:

  • Developing colorectal or endometrial cancer younger than age 50.
  • Developing colorectal cancer, endometrial cancer, or another type of cancer with mismatch repair deficiency (MMR-D) or high-level microsatellite instability (MSI-H) found on testing of the tumor specimen.
  • Developing colorectal cancer and other types of cancer linked with Lynch syndrome separately or at the same time.
  • Colorectal cancer in one or more first-degree relatives who also has or has had another Lynch syndrome-related cancer, with one of these cancers developing before age 50.
  • Colorectal cancer in two or more first- or second-degree relatives with another Lynch syndrome-related cancer.

If a patient has a family history of colon cancer, endometrial cancer, or a related cancer, and/or meets one or more of the criteria listed in the Bethesda guidelines above, doctors may recommend further tests to diagnose Lynch syndrome. 

Tumor Screening Tests

If cancer is already present in the patient or a family member, a small sample of the tumor (a biopsy) can be removed and tested to determine if it was caused by gene mutations related to Lynch syndrome. There are two types of screening tests available:

  • Immunohistochemistry (IHC) Test: This uses a special staining process on tumor samples that indicates the presence or absence of certain proteins. If these proteins are missing, the likelihood of a patient having Lynch syndrome increases.
  • Microsatellite Instability (MSI) Test: This looks for mismatched sequences in stretches of DNA called microsatellites. If two or more of the five markers show instability, a patient is considered to have a greater chance of having Lynch syndrome.

While both of these tests can show an increased likelihood for Lynch syndrome, neither can definitively diagnose it. Instead, patients will need to undergo more specific genetic testing.

Genetic Tests

Genetic testing looks for DNA mutations using either a small sample of blood or a swab from the inside of the mouth. Testing will show one of three possibilities:

  • Positive Result: This indicates a gene mutation associated with Lynch syndrome has been discovered. However, it does not mean a patient has or will have cancer.
  • Negative Result: This indicates a gene mutation associated with Lynch syndrome has not been discovered. However, a patient may still have an increased likelihood of having cancer, especially if they have a family history of cancer.
  • Undetermined Result: This result can occur if a variation is detected that is not associated with Lynch syndrome. In this case, a genetic counselor can help explain the significance of the result.

Treatment

While there is no cure for Lynch syndrome itself, cancer that develops as a result of Lynch syndrome can be treated like normally. This may include the following treatments:

  • Chemotherapy: This uses medication to damage and destroy cancer cells. Rather than targeting a specific area, these drugs travel through the bloodstream and attack cancer cells throughout the body.
  • Radiation Therapy: This uses high-energy waves or particles, such as x-rays, gamma rays, electron beams, or protons, to damage or destroy cancer cells in a specific area.
  • Surgery: This refers to the physical removal of the cancer. The size of the surgery will depend on the stage and location of the cancer. However, Lynch syndrome patients who have colon or endometrial cancer may need to have their entire colon or uterus removed  due to the increased likelihood of recurrence.

Screening & Prevention

Patients with Lynch syndrome who do not have cancer should consider getting regular screening tests to reduce their risk of cancer spreading undetected. The following are general screening recommendations:

  • Colorectal Cancer: Colonoscopy every one to two years starting at age 20, then every year after age 40. If cancer is found, a colectomy (removal of the entire colon) is recommended.
  • Endometrial Cancer: Transvaginal ultrasound and a CA-125 blood test every year beginning at age 30. Some women may also want to consider a total hysterectomy (removal of the entire uterus) to eliminate their risk of endometrial cancer.
  • Stomach and Small Bowel Cancer: Upper endoscopy once every three years starting at age 30.

It is recommended that patients work with their doctor to create a screening plan that is best for them based on their family history of cancer and the specific types of gene mutations they have.

Outlook

Lynch syndrome increases the risk of several types of cancer. The level of risk depends on a variety of factors, such as age, gender, family history, and organ. The following are the general lifetime risks:

  • Colorectal Cancer: 20 to 80 percent
  • Endometrial Cancer: 15 to 60 percent
  • Ovarian Cancer: 1 to 38 percent
  • Stomach Cancer: 1 to 13 percent
  • Hepatobiliary Tract (Liver, Bile Ducts, and/or Gallbladder) Cancer: 1 to 4 percent
  • Urinary Tract Cancer: 1 to 18 percent
  • Small Bowel Cancer: 1 to 6 percent
  • Pancreatic Cancer: 1 to 6 percent
  • Brain or Central Nervous System Cancer: 1 to 3 percent

Next Steps

If you or a loved one has Lynch syndrome, our team of experts is ready to help. Our dedicated Hereditary Colorectal Cancer Center offers the most innovative and comprehensive services available to help identify developing cancers early and treat effectively with a personalized, long-term care plan. Whether you are seeking preventative services or need cancer surgery, our patient-centered care approach will benefit you.

To make an appointment, call (212) 342-1155 or request an appointment online.

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