Lynch syndrome screening: who is tested, what results mean, and colonoscopy ages

What Lynch syndrome is

Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), raises the risk of cancers of the colon and rectum, and of the stomach, small intestine, liver, gallbladder ducts, urinary tract, brain and skin. Women with Lynch syndrome also have an increased risk of cancer of the ovaries and the lining of the uterus (endometrial cancer). In people with Lynch syndrome who develop cancer, it typically occurs in their 40s or 50s. (MedlinePlus Genetics)

Pathogenic variants in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes can cause it. It is typically inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is enough to increase cancer risk, and not all people with Lynch syndrome develop cancer. In the United States, an estimated 1 in 279 people have a variant associated with Lynch syndrome. (MedlinePlus Genetics) It accounts for about 3% of all newly diagnosed colorectal cancers. (NCI PDQ, 2025)

Risk differs by gene. NCI lists these lifetime risks: (NCI PDQ, 2025)

About 1% of people with Lynch syndrome have an EPCAM variant; in one European study their colorectal cancer risk up to age 70 was 75%, comparable to MSH2 carriers. (NCI PDQ, 2025)

Who is offered testing

Doctors judge whether someone is likely to have Lynch syndrome from their personal and family cancer history, and in people diagnosed with certain cancers the cancer cells can be tested. (ACS, Lynch syndrome)

Family history: the Amsterdam criteria. ACS describes them as: (ACS, genetic tests)

• at least 3 relatives have a cancer linked with Lynch syndrome, and
• one is a first-degree relative (parent, brother or sister, or child) of the other 2, and
• at least 2 successive generations are affected, and
• at least 1 relative had their cancer before age 50.

Meeting the Amsterdam criteria does not always mean a person has Lynch syndrome, and many families with Lynch syndrome do not meet them. (ACS, genetic tests)

A person with colorectal cancer: the revised Bethesda guidelines. These include at least one of the following: (ACS, genetic tests)

• diagnosis of colorectal or uterine cancer before age 50;
• a second colorectal cancer, or another cancer linked to Lynch syndrome;
• age under 60, with a cancer that has certain features under a microscope seen with Lynch syndrome;
• a first-degree relative diagnosed before 50 with colorectal cancer or another Lynch syndrome cancer;
• 2 or more first- or second-degree relatives with colorectal cancer or another Lynch syndrome cancer at any age.

Most people who meet the Bethesda criteria do not have Lynch syndrome, and a person can have it and meet none of them. (ACS, genetic tests)

Tumor testing for everyone with colorectal cancer. NCI says universal tumor testing of all colorectal cancers is now recommended as a way to screen for Lynch syndrome, and that with universal testing of all newly diagnosed colorectal cancers, the clinical criteria have been rendered obsolete. Family history and clinical criteria may still help find people who have not had cancer. (NCI PDQ, 2025) The tumor is tested for microsatellite instability (MSI) or for missing mismatch repair (MMR) proteins; if MSI is found or a protein is missing, doctors will most likely recommend genetic testing for Lynch syndrome. Not all people whose cancer shows MSI have Lynch syndrome. (ACS, Lynch syndrome)(ACS, genetic tests)

NICE (UK). NICE recommends offering testing to all people with colorectal cancer when first diagnosed, using immunohistochemistry for mismatch repair proteins or microsatellite instability testing, followed by further tests (BRAF V600E and MLH1 promoter hypermethylation) and then confirming Lynch syndrome by genetic testing of germline DNA. (NICE HTG430) It also recommends offering testing for Lynch syndrome to people diagnosed with endometrial cancer, starting with immunohistochemistry. (NICE HTG557)

Other reasons. NCI says clinical practice guidelines recommend genetic testing for anyone diagnosed with colorectal cancer before age 50, and that a family member with a known inherited harmful genetic change, or family members with colon cancer and endometrial cancer, are features that suggest a hereditary syndrome. (NCI, genetic testing) See how to collect your family health history.

What a germline test result means

A germline test looks at inherited DNA, usually from blood or saliva, and results usually come back in about 2 to 3 weeks. It is different from tumor testing, which looks for changes that occurred during a person's lifetime. (NCI, genetic testing) NCI describes the possible results this way: (NCI, genetic testing)

• Positive: the lab found a pathogenic or likely pathogenic variant, a genetic change associated with increased cancer risk. It may lead to being checked at a younger age or more often.
• True negative: the family's known variant was not found. The risk is probably the same as that of someone in the general population, not zero.
• Uninformative negative: no harmful change was found in a person with a strong family history, but none has been found in the family either. The family may still have an undetected variant, so follow-up is based on personal and family history.
• Variant of uncertain significance (VUS): not enough data to know whether it raises cancer risk. Most are later reclassified as benign, so a VUS is typically not used in health care decisions; stay in touch with the provider who did the testing for updates.

NICE says people should be told the possible implications of test results for both themselves and their relatives, and that genetic testing should be discussed by a health care professional with appropriate training. (NICE HTG430) The same result types are explained on BRCA genetic test results.

Colonoscopy ages and intervals by gene

Lynch syndrome speeds up the change from normal lining to polyp to cancer, which is why screening is done with colonoscopy at shorter intervals. (NCI PDQ, 2025) Most organizations tailor their advice to each gene. NCI summarizes the US NCCN guideline and the UK guideline this way: (NCI PDQ, 2025)(BSG, 2020)

NCI notes that all of these schedules assume the findings are normal, and that a more aggressive schedule might be considered for an individual. (NCI PDQ, 2025) If polyps are found, see colonoscopy after polyps for how follow-up intervals work in general, and what to expect at a colonoscopy.

Other cancers

• Endometrial cancer: NCI says endometrial cancer screening has been suggested for women with Lynch syndrome who have not had a risk-reducing hysterectomy, with transvaginal ultrasound (not recommended before menopause) and/or endometrial biopsy proposed, but that current NCCN guidelines suggest these methods may not benefit women with Lynch syndrome. (NCI PDQ, 2025) ACS says women with Lynch syndrome may be advised to start screening for endometrial cancer. (ACS, Lynch syndrome)
• Stomach, small bowel and pancreas: the UK guideline recommends surveillance of these only within a clinical trial, and recommends screening for H. pylori in people with Lynch syndrome. (BSG, 2020) See stomach cancer screening and pancreatic cancer screening.

Where they differ:

• Start age for MLH1 and MSH2: NCCN says 20 to 25 (or earlier with a very young family diagnosis); the UK guideline says 25. (NCI PDQ, 2025)(BSG, 2020)
• Start age for MSH6 and PMS2: NCCN says 30 to 35; the UK guideline says 35. (NCI PDQ, 2025)(BSG, 2020)
• Interval: NCCN says every 1 to 2 years for MLH1, MSH2 and EPCAM and every 1 to 3 years for MSH6 and PMS2; the UK guideline says every 2 years for all, until age 75. (NCI PDQ, 2025)(BSG, 2020)
• US Multi-Society Task Force (2014): one schedule for all genes: colonoscopy beginning at 20 to 25, or 2 to 5 years before the earliest colorectal cancer if before 25, repeated every 1 to 2 years; it adds that starting at 30 for MSH6 and 35 for PMS2 may be considered. (NCI PDQ, 2025)
• ACS: for families known to carry a Lynch syndrome change, colonoscopy during the early 20s or 2 to 5 years younger than the youngest person diagnosed, whichever is earlier, every 1 or 2 years; this includes relatives who have not been tested. (ACS, genetic tests)
• Who is tested: NICE recommends testing all people with colorectal or endometrial cancer; ACS and NCI also describe criteria based on age and family history. (NICE HTG430)(NICE HTG557)(ACS, genetic tests)(NCI, genetic testing)

Your doctor decides what your result means for you.

This page does not give treatment advice. If you have an abnormal result, see after an abnormal screening result for questions to ask.

Questions people ask

What is Lynch syndrome?

Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, including colorectal cancer and, in women, cancer of the ovaries and the lining of the uterus. Pathogenic variants in the MLH1, MSH2, MSH6, PMS2 or EPCAM genes can cause it. (MedlinePlus Genetics)

How common is Lynch syndrome?

MedlinePlus Genetics says it is estimated that 1 in 279 people in the United States have a genetic variant associated with Lynch syndrome. NCI says it accounts for about 3% of all newly diagnosed colorectal cancers. (MedlinePlus Genetics) (NCI PDQ, 2025)

Who should think about testing for Lynch syndrome?

ACS says doctors often use the Amsterdam criteria (family history) and the revised Bethesda guidelines (for people with colorectal cancer). NCI says universal tumor testing of all colorectal cancers is now recommended, and NICE recommends testing for everyone diagnosed with colorectal or endometrial cancer. (ACS, genetic tests) (NCI PDQ, 2025) (NICE HTG430) (NICE HTG557)

When does colonoscopy start for people with Lynch syndrome?

It depends on the gene and the guideline. NCCN (as summarized by NCI) says age 20 to 25 for MLH1, MSH2 and EPCAM and 30 to 35 for MSH6 and PMS2. The UK BSG guideline says age 25 for MLH1 and MSH2 and 35 for MSH6 and PMS2, every 2 years until 75. (NCI PDQ, 2025) (BSG, 2020)

Should relatives be tested too?

ACS says close relatives (parents, siblings and children) of a person with a Lynch syndrome gene change have a 50/50 chance of having the same change. In families known to carry one, doctors recommend that relatives who tested positive and relatives who have not been tested start colonoscopy in their early 20s, or 2 to 5 years younger than the youngest person in the family with a diagnosis. (ACS, Lynch syndrome) (ACS, genetic tests)

Related

• Endometrial cancer screening: tests and results
• Family history: when screening starts earlier
• BRCA genetic test results
• Colonoscopy after polyps
• Colorectal cancer screening tests compared
• After an abnormal screening result