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Lynch syndrome

  • An inherited genetic disorder linked to an increased risk of developing cancer earlier in life
  • Risk factors include family history or early diagnosis of colorectal cancer or endometrial cancer
  • Regular cancer screening or preventive surgery may reduce risk of some cancers
  • Involves gastrointestinal cancer program and GI cancer and genetics prevention program

Lynch syndrome


Lynch syndrome is an inherited genetic disorder linked to an increased risk of developing cancer, often at a younger age in life—especially colorectal cancer, and, for women, endometrial cancer. While those are the most common types of cancer associated with the disorder, it is also tied to a greater lifetime risk of other types of cancer as well, including stomach, small intestine, liver, ovarian, upper urinary tract, gallbladder ducts, brain, and skin.

Not everyone with Lynch syndrome will inevitably develop cancer. Your risk depends, in part, on which of the five Lynch syndrome-responsible genes has the inherited genetic defect and the types of cancer that have been diagnosed throughout your family’s medical history. For perspective, Lynch syndrome accounts for about 3 percent of colorectal cancers and 2 percent of endometrial cancers.

Lynch syndrome is one of the few “Tier 1 genomic conditions” included in a list that the Centers for Disease Control and Prevention (CDC) promotes as genetic conditions that can and should be monitored to improve or prevent health issues. The earlier a person is aware of the condition, the more opportunities exist to take preventative actions to reduce the risk of developing cancer.

Genetic testing for Lynch syndrome is recommended for people with an immediate family member who has been diagnosed with it, as well as for those who have a family history of early cancer diagnoses or clustering of some cancer types.

“Genetic testing is key in evaluating patients who are at risk for an inherited cancer syndrome, such as Lynch syndrome. Mutations in particular genes are linked to specific cancer risks,” says Xavier Llor, MD, director of the GI Cancer Prevention Program.

“There are screening and cancer preventive strategies that have been proven to decrease cancer-related disease and death in these cases. It is key to proceed with genetic testing so these strategies can be implemented when a mutation is found,” Dr. Llor says.

At Yale Medicine, our medical care teams help families navigate the options available, including advising patients on the appropriate cancer screening procedures and whether more invasive preventative actions, such as surgery, should be considered.

Who is at risk for Lynch syndrome?

The strongest indicator of a person’s risk of Lynch syndrome is having family members with Lynch syndrome or having had some specific cancers, particularly at younger than usual ages. A parent with Lynch syndrome has a 50 percent chance of passing it on to each child.

Other risks include a colorectal cancer or endometrial cancer diagnosis before age 50.

What causes Lynch syndrome?

Lynch syndrome is caused by a genetic variant, or mutation, in five genes: MLHL1MSH2MSH6PMS2, and EPCAM. Collectively, these are referred to as “DNA mismatch repair genes.” They play a role in repairing mistakes that can be made after DNA is copied for new cells created in the body. 

Who should have genetic testing done?

If one or more of the criteria below is met, consider seeking genetic counseling and testing: 

  • Family member with a confirmed diagnosis of Lynch syndrome
  • Colorectal and endometrial cancer diagnosis at any age, particularly after pathology testing shows alterations related to Lynch syndrome
  • Multiple primary cancer diagnoses
  • Several family members have had cancers related to Lynch syndrome

How is Lynch syndrome diagnosed?

Lynch syndrome is diagnosed through genetic testing or tumor screening. 

Genetic testing. Your doctor may recommend genetic testing for multiple genes associated with the disorder. A genetic test can result in one of the following:

  • Positive: If a genetic variant is found, you have a mutation associated with Lynch syndrome.
  • Negative:  This means a genetic variant known to cause Lynch syndrome was not found.
  • Variant of Unknown Significance (VUS):  A genetic mutation was found in one of the genes associated with Lynch syndrome, but it’s uncertain if that particular mutation causes cancer. 

Tumor screening. When colorectal or endometrial cancer is diagnosed, it’s common practice to have the tumor tissue examined, or screened, to see if Lynch syndrome might have been the cause. There are two types of tumor screening methods:

  • Immunohistochemistry (IHC) screening: This test looks for the presence or absence of the proteins synthesized by the Lynch syndrome genes: MLH1, PMS2, MSH2, or MSH6.  
  • Microsatellite Instability (MSI) screening: Microsatellites are pieces of DNA that can show—on the basis of length—if the mismatch repair process is not working well, an indication of Lynch syndrome. 

What can be done to lower the risk of cancers caused by Lynch syndrome?

Regular cancer screening to detect cancer early or preventative surgery to reduce risk of developing some cancers are two important ways to lower the risk of cancers caused by Lynch syndrome. “Daily use of aspirin has been proven to reduce cancer risk in Lynch syndrome,” Dr. Llor says. “Keeping healthy habits such as regular exercise, a diet rich in fruits and vegetables and less red meat, and keeping the weight in check can help reduce the risk of cancer in Lynch syndrome, too.”  

Cancer screening:

  • Colon. People with Lynch syndrome typically start colonoscopy screenings in their 20s, repeating them every year or two years. Because some tumors associated with colon cancer can be difficult to detect, the type of technology used for a colonoscopy matters. High-definition colonoscopy is usually recommended. “But the most important factors for tumor detection are very good bowel preparation and sufficient time spent by the endoscopist doing the procedure,” Dr. Llor says.
  • Endometrial. Women may be advised to have an endometrial biopsy performed each year.
  • Ovarian. An annual blood test and ultrasound can be used for detecting early signs of cancer for women.
  • Urinary tract and bladder. Periodic urine samples and ultrasounds can help monitor for signs of blood and cancerous cells.
  • Gastrointestinal. An endoscopy can be performed on the stomach and small intestines at a frequency determined by you and your doctor.

Preventative surgery: After thoroughly evaluating the potential risks and benefits of surgery, preventative surgery to reduce your risk of developing cancer is an option.

  • Hysterectomy and/or oophorectomy. This surgery removes the uterus and/or the ovaries, which would reduce a woman’s chances of developing endometrial or ovarian cancer.
  • Colectomy. This surgery removes the colon, which can be an option for someone who is unable or unwilling to go through frequent colon screening. 

How is Yale Medicine unique in its approach to caring for patients with Lynch syndrome?

“The GI Cancer Prevention Program has a holistic approach to inherited cancer syndromes,” Dr. Llor says. “We provide specific advice on cancer preventive measures, family planning, and any other aspects relevant to patients with Lynch syndrome.”