Lynch Syndrome: Definition

by Jason Wasserman MD PhD FRCPC
March 23, 2026

Lynch syndrome is an inherited condition that significantly increases the risk of developing several types of cancer, most commonly colorectal (colon and rectal) cancer and endometrial (uterine) cancer. It is caused by an inherited change in one of the genes responsible for making mismatch repair (MMR) proteins — a group of proteins that normally find and fix mistakes in a cell’s DNA. When one of these proteins is missing or not working properly, DNA errors can accumulate over time, increasing the risk of cancer. Lynch syndrome is the most common inherited cause of colorectal cancer.

Lynch syndrome is sometimes referred to by an older name, hereditary nonpolyposis colorectal cancer (HNPCC), though this term is used less often today.

What causes Lynch syndrome?

Lynch syndrome is caused by an inherited mutation (change) in one of four genes: MLH1, MSH2, MSH6, or PMS2. These genes encode mismatch repair proteins. Mutations in MLH1 and MSH2 are the most common and are generally associated with a higher lifetime cancer risk. Mutations in MSH6 and PMS2 are less common and may be associated with a somewhat different cancer risk profile.

Lynch syndrome follows an autosomal dominant inheritance pattern, meaning that inheriting just one mutated copy of the gene — from either parent — is enough to cause the syndrome. Each child of a person with Lynch syndrome has a 50% chance of inheriting the mutation.

It is important to understand that having a Lynch syndrome mutation does not mean cancer is inevitable. It means the lifetime risk of certain cancers is significantly higher than average. Many people with Lynch syndrome live long, healthy lives with appropriate surveillance and cancer screening.

What cancers are associated with Lynch syndrome?

Lynch syndrome is associated with an increased risk of several types of cancer. The most common are:

• Colorectal (colon and rectal) cancer – The most common Lynch syndrome-associated cancer. People with Lynch syndrome often develop colorectal cancer at a younger age than the general population, sometimes before age 50.
• Endometrial (uterine) cancer – In women with Lynch syndrome, endometrial cancer is the second most common cancer associated with the syndrome, and in some cases, may be the first cancer to develop.
• Ovarian cancer – Women with Lynch syndrome have an increased risk, though lower than for colorectal or endometrial cancer.
• Gastric (stomach) cancer
• Cancer of the small intestine
• Cancer of the urinary tract (including the renal pelvis and ureter)
• Bladder cancer
• Pancreatic cancer
• Brain tumours (most often glioblastoma, seen in a rare variant called Turcot syndrome)
• Sebaceous skin tumours (see Muir-Torre syndrome below)

The specific cancers and level of risk depend in part on which gene is mutated. A genetic counsellor can provide personalized risk estimates based on the specific mutation involved.

How is Lynch syndrome diagnosed?

Lynch syndrome is usually suspected when a tumour is found to be mismatch repair deficient (dMMR) on pathology testing. This can be identified using immunohistochemistry (IHC), which tests whether the four MMR proteins are present in the tumour cells. If one or more proteins are missing, further testing is usually done to determine whether the loss is due to Lynch syndrome or a non-inherited (sporadic) cause.

When MLH1 is the protein that is lost, an additional test called MLH1 promoter methylation testing is often performed. If MLH1 methylation is present, the loss is usually due to a sporadic, non-inherited change in the tumour rather than Lynch syndrome. If methylation is absent, Lynch syndrome becomes more likely, and germline genetic testing is recommended.

A confirmed diagnosis of Lynch syndrome requires germline genetic testing — a test performed on a blood or saliva sample — to look for an inherited mutation in one of the four MMR genes. This testing is typically arranged through a genetic counsellor or medical genetics service.

What is Muir-Torre syndrome?

Muir-Torre syndrome is considered a variant of Lynch syndrome. People with Muir-Torre syndrome carry a mutation in an MMR gene — most often MSH2 — and are at increased risk of developing distinctive skin tumours in addition to the internal cancers associated with Lynch syndrome.

These skin tumours include:

• Sebaceous carcinoma – A rare type of skin cancer arising from the oil-producing (sebaceous) glands of the skin, most commonly around the eyelid or face.
• Sebaceous adenomas – Non-cancerous tumours of the sebaceous glands. Multiple sebaceous adenomas, particularly in a younger person, should raise suspicion for Muir-Torre syndrome.
• Keratoacanthomas – Rapidly growing skin tumours that may resemble squamous cell carcinoma. When multiple keratoacanthomas occur, they can also be a feature of Muir-Torre syndrome.

The development of sebaceous skin tumours — especially if multiple or occurring at a younger age — may be the first sign that leads to a diagnosis of Muir-Torre syndrome and underlying Lynch syndrome.

What happens after a Lynch syndrome diagnosis?

A diagnosis of Lynch syndrome has important implications for both the patient and their family. People with Lynch syndrome are typically referred to a specialist for a personalised surveillance plan, which may include:

• Regular colonoscopies, often starting at a younger age and performed more frequently than standard screening.
• Gynaecological surveillance for women, which may include regular ultrasound and endometrial sampling.
• Consideration of risk-reducing surgery in some cases, such as the removal of the uterus and ovaries after completing a family.
• Surveillance for other Lynch syndrome-associated cancers based on the specific gene mutation and family history.

Because Lynch syndrome is inherited, first-degree relatives (parents, siblings, and children) have a 50% chance of carrying the same mutation and should be offered genetic testing. Identifying Lynch syndrome in a family allows at-risk relatives to begin appropriate screening before cancer develops, which can be life-saving.

Questions to ask your doctor

• Has my tumour been tested for mismatch repair deficiency, and what were the results?
• Should I be referred for germline genetic testing for Lynch syndrome?
• Which gene mutation do I have, and how does it affect my cancer risk?
• What cancer surveillance plan is recommended for me?
• Should my family members be tested, and how can they access genetic counselling?
• Are there any steps I can take to reduce my cancer risk?