What is Lynch syndrome and should I be tested for it?

Lynch syndrome is an inherited condition that increases your risk of developing certain cancers, especially bowel cancer (also called colorectal cancer) and womb cancer (endometrial cancer). It’s caused by changes in genes that normally repair mistakes in your DNA. When these repair genes don’t work properly, cells accumulate errors that can lead to cancer.

Around 1 in 300 people are estimated to carry Lynch syndrome, making it one of the most common hereditary cancer conditions. Yet most people who have it don’t know - the great majority of carriers have never been diagnosed. Knowing you carry Lynch syndrome allows you to have more frequent screening that can catch cancers early, when they’re most treatable, and in some cases prevent them from developing at all.

What causes Lynch syndrome?

Lynch syndrome happens when you inherit a faulty copy of one of four main DNA-repair genes: MLH1, MSH2, MSH6, or PMS2. (A fifth gene, EPCAM, can also cause Lynch syndrome when deletions affect the neighbouring MSH2 gene.) These genes produce proteins that form the “mismatch repair” system - a quality-control mechanism that fixes copying errors whenever your cells divide.

When one of these genes carries a pathogenic variant (a harmful change), the repair system doesn’t work as well. Over time, uncorrected errors build up in cells lining the bowel, womb, and other tissues. Some of these errors eventually turn healthy cells cancerous.

Lynch syndrome follows an autosomal dominant inheritance pattern. That means:

• If one parent carries a Lynch syndrome variant, each of their children has a 50% chance of inheriting it.
• You only need one faulty copy (from one parent) to have Lynch syndrome.
• Men and women are equally likely to inherit and pass on the condition.
• The syndrome can appear to “skip” generations if a carrier never develops cancer or dies of other causes before cancer appears.

Which cancers does Lynch syndrome increase risk for?

People with Lynch syndrome have a higher lifetime risk of several cancers. The exact figures vary considerably depending on which gene is affected, and more recent gene-specific estimates tend to be lower than the older textbook ranges:

• Bowel (colorectal) cancer: the most common Lynch-related cancer. Estimates of lifetime risk range widely - roughly 10% to 50% or more depending on the gene involved, compared with around 1 in 15 to 1 in 20 in the general UK population. The average age of diagnosis is much younger than usual, around the mid-40s for the higher-risk genes, compared with most general-population cases occurring after age 60.
• Womb (endometrial) cancer: women with Lynch syndrome have a lifetime risk of around 35–46% depending on the gene, versus roughly 3% for women generally.
• Ovarian cancer: around 10–17% lifetime risk (general population: under 1%).
• Stomach cancer: up to around 15% lifetime risk for the higher-risk genes.
• Urinary tract cancers (kidney, ureter, bladder): broadly in the region of 1–16% depending on sex and gene.
• Small bowel, pancreas, bile duct, brain, and sebaceous skin tumours: all increased but less common.

The exact risks depend on which gene is affected. MLH1 and MSH2 variants generally carry the highest cancer risks; MSH6 and PMS2 variants often have lower (though still elevated) risks, and cancers tend to appear at older ages.

What are the signs that Lynch syndrome might run in my family?

You should consider genetic testing if:

• You or a close relative (parent, sibling, child) developed bowel or womb cancer before age 50.
• Multiple relatives on the same side of the family have had bowel, womb, ovarian, stomach, or urinary-tract cancers - especially if diagnosed younger than average.
• You’ve had more than one Lynch-related cancer yourself (for example, bowel cancer followed years later by womb cancer).
• A relative has already been diagnosed with Lynch syndrome.
• Tumour testing on a bowel or womb cancer showed “mismatch repair deficiency” or “microsatellite instability” - laboratory features that suggest Lynch syndrome.

NICE guidance recommends that everyone diagnosed with colorectal cancer should have their tumour tested for mismatch-repair deficiency when first diagnosed. If the tumour shows this signature, further testing is offered to confirm Lynch syndrome and identify the specific gene involved.

How is Lynch syndrome diagnosed?

Diagnosis involves a blood test or saliva sample that looks for pathogenic variants in the mismatch-repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). In NHS clinical genetics services, testing is usually prompted by:

1. A strong family history of Lynch-related cancers.
2. Tumour testing (immunohistochemistry or microsatellite instability testing) on a cancer specimen showing mismatch-repair deficiency.
3. Meeting Amsterdam II or revised Bethesda clinical criteria - sets of family-history rules that identify high-risk individuals.

If a variant is found, your relatives can then have predictive testing to see whether they’ve inherited the same variant. Relatives who test negative can return to standard population screening. Those who test positive can enter enhanced surveillance.

What happens if I test positive?

If you carry a Lynch syndrome variant, your doctors will recommend:

• Regular colonoscopy (bowel camera examination), typically every 1–2 years and usually starting around age 25 (or earlier if there is a young cancer diagnosis in your family). Colonoscopy can detect and remove pre-cancerous polyps before they turn into cancer.
• For women: regular review and, where appropriate, ultrasound and sometimes endometrial biopsy to screen for womb and ovarian cancer, often starting around age 30–35. Some women choose risk-reducing surgery (hysterectomy and removal of ovaries and fallopian tubes) once they’ve completed their family, which substantially lowers cancer risk.
• Aspirin: NICE recommends considering daily aspirin, taken for more than two years, to help reduce bowel-cancer risk in people with Lynch syndrome. The main clinical trial (CAPP2) used a relatively high daily dose, and the optimal dose is still being studied, so this should always be started after discussion with your GP or specialist, as aspirin carries a small bleeding risk.
• Genetic counselling before and after testing, so you understand what the result means for you and your family.

Enhanced screening doesn’t eliminate cancer risk, but studies suggest it substantially reduces it and helps catch cancers at earlier, more curable stages. Long-term studies of regular colonoscopy in Lynch-syndrome families have reported large reductions in bowel-cancer cases and deaths.

Who should consider genetic testing?

Genetic testing for Lynch syndrome is appropriate if:

• You meet the family-history criteria above.
• You’ve been diagnosed with a Lynch-related cancer and tumour testing suggests hereditary causes.
• A relative has tested positive for a Lynch syndrome variant.
• You’re planning a family and have a significant family history of early-onset bowel or womb cancer - knowing your status can inform decisions and allow early surveillance.

The NHS offers genetic testing free when clinical criteria are met, typically through referral to a regional genetics service. Private genetic testing (such as hereditary cancer panels) is also available and may be faster or more comprehensive - covering Lynch genes alongside many other cancer-predisposition genes - but won’t automatically include NHS follow-up surveillance unless results are shared with your GP and trigger a genetics referral.

What you can do at Jeen

Jeen’s Cancer Risk Screening analyses 50 genes associated with hereditary cancer risk, including the main Lynch syndrome mismatch-repair genes (MLH1, MSH2, MSH6, PMS2). The test includes 45-minute specialist genetic counselling to help you understand your family history, interpret results, and plan next steps. You can collect your sample at home using a buccal (cheek) swab, or we can arrange a blood draw at a partner collection point (+£40) or a home-nurse visit (+£65), and results arrive within 17-21 working days from when your sample reaches the laboratory. Variant interpretation follows NHS Genomic Medicine Service standards, so if a pathogenic variant is found, your report can be shared with your GP to access NHS surveillance.

If you’re also planning a family, our Combined Cancer + Carrier Screening bundles the 50-gene hereditary-cancer panel with a 1,008-gene carrier-screening panel. You’ll get one counselling session, one report, and insights into both your own cancer predisposition and any recessive conditions you might pass to children - better value than ordering the tests separately.

Genetic testing won’t change the past, but it can change the future. Knowing whether you carry Lynch syndrome allows you and your relatives to take control through earlier, more effective screening.