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What is Lynch Syndrome?

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is a type of inherited cancer syndrome associated with a genetic predisposition to different cancer types. This means people with Lynch syndrome have a higher risk of certain types of cancer.    

Cancer begins when normal cells begin to change and grow out of control, forming a mass called a tumor.  A tumor can be benign (non-cancerous) or malignant (cancerous), which means it can spread to other parts of the body. A benign tumor means the tumor can grow but will not spread.

People who have Lynch syndrome have a significantly increased risk of developing colorectal cancer. There is also an increased risk of developing other types of cancers, such as endometrial (uterine)stomachbreastovariansmall bowel (intestinal),pancreaticprostateurinary tractliverkidney, and bile duct cancers.

Lynch syndrome is among the most common hereditary cancer syndromes, and estimates suggest as many as 1 in every 300 people may be carriers of an alteration in a gene associated with Lynch syndrome. Clues to whether there is Lynch syndrome in a family include diagnoses of colorectal and/or endometrial cancer in multiple relatives on the same side of a family. In addition, cancers associated with Lynch syndrome are more likely to be diagnosed at a young age. People with Lynch syndrome are also at an increased risk of developing multiple types of cancers during their lifetime.

ASCO recommends that tumor testing for Lynch syndrome be performed in all people diagnosed with colorectal cancer and recent guidelines recommend tumor testing for all endometrial cancers as well.

What causes Lynch syndrome?

Lynch syndrome is a genetic condition. This means that the cancer risk can be passed from generation to generation in a family. These types of mutations are called inherited, or germline, mutations. Alterations in several genes involved in DNA mismatch repair that have been linked to Lynch syndrome. They include the genes of  MLH1,  MSH2,  MSH6,  PMS2,  and  EPCAM. A mutation (alteration) in any of these genes gives a person an increased lifetime risk of developing colorectal cancer and other related cancers. Women also have an increased risk of developing endometrial and ovarian cancers.


Not all families that appear to have Lynch syndrome will have identifiable alterations in  MLH1,  MSH2,  MSH6,  PMS2,  or  EPCAM. Research is ongoing to identify other genes associated with Lynch syndrome. Some people will develop changes in these genes that are not inherited but occur due to the body’s aging process and other causes that are not well understood. These types of mutations are called acquired. If a tumor is found to have alterations in these genes, the person’s blood will also be tested for that abnormal gene. If the blood and tumor both have the changed gene, the condition is inherited rather than acquired, meaning other family members could be affected.

What are the signs of Lynch syndrome?

A set of criteria used to help doctors decide who should be tested for Lynch syndrome is called the revised Bethesda guidelines, which are listed below:

  • Developing colorectal or endometrial cancer younger than age 50

  • Developing colorectal cancer, endometrial cancer, or other 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 1 or more first-degree relatives who also has or has had another Lynch syndrome-related cancer*, with 1 of these cancers developing before age 50. The phrase “first-degree relatives” include parents, siblings, and children.

  • Colorectal cancer in 2 or more first- or second-degree relatives with another Lynch syndrome-related cancer*. “Second-degree relatives” include aunts, uncles, grandparents, grandchildren, nephews, and nieces. 

    *(colorectal cancer, endometrial cancer, ovarian cancer, stomach cancer, small bowel cancer, ureter or renal pelvis cancer, bladder cancer, bile duct cancer, pancreatic cancer, or sebaceous adenomas of the skin)


The definition of Lynch syndrome is still evolving. A person may still have Lynch syndrome even if the revised Bethesda guidelines do not fully match the family history. Therefore, meeting with a health professional who has training in genetic diseases and conditions is recommended for people who have a family history that suggests the possibility of Lynch syndrome.

How is Lynch syndrome diagnosed?

Lynch syndrome can be confirmed through a blood test. The test can determine if someone carries a mutation that can be passed down (called heritable) in 1 of the genes associated with Lynch syndrome. Currently, testing is available for the MLH1, MSH2, MSH6, PMS2 andEPCAM genes. However, not all families with Lynch syndrome will have an identifiable mutation in 1 of these genes.

Screening tests can also be performed on tumor (cancer) tissue to determine if Lynch syndrome is likely. The 2 screening tests suggested are microsatellite instability testing (MSI) and immunohistochemistry testing (IHC). The results of these tests can indicate whether more specific genetic testing should be considered.

How is Lynch syndrome inherited?

Normally, every cell has 2 copies of each gene: 1 inherited from the mother and 1 inherited from the father. Lynch syndrome follows an autosomal dominant inheritance pattern, in which a mutation needs to happen in only 1 copy of the gene for the person to have an increased risk of getting that disease. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having the same mutation.  However, if the parents test negative for the mutation, the risk to the siblings significantly decreases but their risk may still be higher than an average risk.

Options exist for people interested in having a child when a prospective parent carries a gene mutation that increases the risk for this hereditary cancer syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the mutation. A woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and is tested for the hereditary condition in question. People can then choose to transfer embryos that do not have the genetic mutation. PGD has been in use for over 2 decades and has been used for several hereditary cancer predisposition syndromes. However, this is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic.

What are the estimated cancer risks associated with Lynch syndrome?

General lifetime cancer risks for people with Lynch syndrome

  • Colorectal cancer                                                            20% to 80%

  • Stomach cancer                                                               1% to 13%

  • Hepatobiliary tract cancer (liver/bile duct)                    1% to 4%

  • Urinary tract (renal pelvis, ureter, bladder) cancer        1% to 18%

  • Small bowel cancer (intestines)                                      1% to 6%

  • Pancreatic cancer                                                             1% to 6%

  • Brain or central nervous system tumor                           1% to 3%

Cancer risks for women with Lynch syndrome

  • Endometrial cancer                                                           15% to 60%

  • Ovarian cancer                                                                   1% to 38%

What are the cancer screening options for Lynch syndrome?

ASCO recommends the following screening for people with Lynch syndrome. It is important to discuss these options with your doctor, as each individual is different:

General screening and risk-reduction guidelines

  • Colonoscopy every 1 to 2 years, beginning between the ages of 20 to 25 or 5 years younger than the earliest age at diagnosis in the family, whichever is sooner

  • Upper endoscopy every 3 to 5 years, in addition to testing for Helicobacter pyloriinfection at a baseline exam with treatment if positive

  • Annual total body skin examination

  • Consideration of a daily aspirin, which has been linked to a reduced risk of colorectal cancer and possibly other cancers in individuals with Lynch syndrome

  • Screening for other cancers linked with Lynch syndrome may be recommended depending on a person’s family history, though the effectiveness of such screening remains unproven.


Screening for women

  • Yearly pelvic examination, pelvic ultrasound, endometrial biopsy, from age 30 to 35. Women who are finished having children may want to consider having preventive surgery to remove the uterus and ovaries, especially since screening for endometrial and ovarian cancer has never proven to be effective in women with Lynch syndrome.


Screening options may change over time as new technologies are developed and more is learned about Lynch syndrome and its other forms. It is important to talk with your doctor about appropriate screening tests.

Questions to ask the health care team

If you are concerned about your risk of colorectal cancer or other types of cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing colorectal cancer or other types of cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think your family may have Lynch syndrome, consider asking the following questions:

  • Does my family history increase my risk of colorectal cancer or other types of cancer?

  • Does my family history increase my risk of skin cancer or other skin problems?

  • Have MSI or IHC tests been done on my tumor tissue?

  • Should I meet with a genetic counselor?

  • Should I consider genetic testing?

 Originally published by the American Society of Clinical Oncology  ©ASCO. All Rights Reserved 

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