Lynch syndrome: inherited bowel and womb cancer risk

Lynch syndrome used to be called hereditary non-polyposis colorectal cancer, or HNPCC. The older name hints at a difference from familial adenomatous polyposis: people with Lynch syndrome do not usually grow hundreds of polyps, yet they are still at increased risk of bowel cancer. It arises from a harmful inherited change in one of the genes that run the cell's DNA mismatch repair system, which acts like a proofreader for copying errors.

NHS England says the syndrome does not directly cause cancer. Instead the genetic changes allow more abnormal cells to develop, and those cells multiply and raise the chance of cancer. Bowel cancer is the best known consequence, with womb (endometrial) cancer the other leading one. The NHS Genomics Education Programme also lists ovarian, pancreatic and bile duct, stomach, small intestine, brain, urinary tract and skin cancers, and Cancer Research UK adds gallbladder and prostate.

People with Lynch syndrome who develop bowel cancer tend to do so earlier than other people, and NHS England notes a link with developing more than one cancer over a lifetime.

Four mismatch repair genes are involved, MLH1, MSH2, MSH6 and PMS2, plus EPCAM, whose deletion can silence the neighbouring MSH2 gene. Rarely, Lynch syndrome is caused by a chemical tag that switches off MLH1 from birth rather than a change in the DNA letters.

Inheritance is autosomal dominant. Think of each person as carrying two copies of every gene, one from each parent. A parent with Lynch syndrome has one working and one faulty copy of a mismatch repair gene, and a child receives one of the two at random. Sons and daughters are equally likely to inherit it, and so are brothers and sisters of an affected person. The NHS Genomics Education Programme gives the chance as 50%, or 1 in 2, for each child and sibling.

Inheriting the change is not the same as getting cancer. Not everyone who carries it develops a cancer, and the exact risks depend on which gene is involved. This is why the genetics team gives gene-specific advice rather than one set of numbers.

Since April 2023, NHS England says everyone diagnosed with bowel or endometrial cancer is offered tumour testing that can point towards Lynch syndrome. NICE recommends this screening at first diagnosis, using either immunohistochemistry for the mismatch repair proteins or testing for microsatellite instability, and the NHS Genomics Education Programme explains that a blood test for the inherited gene change follows if the tumour result suggests it.

A diagnosis helps in two ways. It guides cancer treatment, because NHS England notes that bowel cancers in people with Lynch syndrome tend to respond to immunotherapy such as pembrolizumab. It also identifies relatives. Those who test positive are referred to genetic services to discuss surveillance and prevention.

Others come to testing through a family history of bowel and related cancers. A family-wide pattern, rather than a single case, is what usually raises suspicion. Because many carriers are unaware, the NHS Genomics Education Programme says that as many as 95% of people with Lynch syndrome do not know they have it.

Guidance summarised by the NHS Genomics Education Programme is based on the British Society of Gastroenterology and UK Cancer Genetics Group. Bowel cancer surveillance is by colonoscopy every two years from age 25 or 35 depending on the gene. A national bowel cancer screening programme for Lynch syndrome launched in 2024, with colonoscopies at local centres by specially trained staff. Around 10,000 people were expected to be invited that year.

• Aspirin: daily aspirin has been shown to reduce the risk of bowel and certain other cancers. The UK Cancer Genetics Group recommends 150 mg once daily, though people over 70 kg may benefit from more, and the best dose is still being studied in the CAPP3 trial.

• Stomach: testing for and treating Helicobacter pylori is advised, particularly before starting aspirin, to reduce stomach cancer risk.

• Womb and ovaries: women who have completed their family may consider surgery to remove the womb, tubes and perhaps ovaries after 35. Hormone replacement therapy is usually recommended after ovary removal until the age of natural menopause.

• Prostate: the role of PSA and MRI screening is uncertain, though targeted PSA screening has support for carriers of MSH2 or MSH6 changes.

• Other cancers: routine screening for cancers outside the bowel has not been shown to be effective, so the emphasis is on symptom awareness and prompt investigation. Diet, smoking and alcohol advice also applies.

Parents who carry a mismatch repair variant can ask a clinical genetics service about the options. The Human Fertilisation and Embryology Authority has approved pre-implantation genetic testing (PGT-M) for Lynch syndrome. Other options listed by the NHS Genomics Education Programme include prenatal testing, donor gametes, adoption, or conceiving naturally and testing children later in life.

Because every first-degree relative has a 1 in 2 chance of carrying the change, cascade testing is a central part of care. The NHS England programme explicitly invites relatives of people with a positive result to be tested.

Children are generally not tested for cancer genes before adulthood, because Cancer Research UK explains that testing is meant to be an informed personal choice and bowel surveillance does not start until the mid-twenties or later.

Many people describe relief at having a plan after years of uncertainty about family cancers, alongside worry. The aim of the NHS pathway is for a diagnosis to be linked to lifelong, regular care rather than a one-off result.

Support and information are available from Lynch Syndrome UK, Cancer Research UK (including its Lynch Choices resource) and Macmillan, which are the patient resources signposted by the NHS Genomics Education Programme. A genetic counsellor can also explain what the result means for your own plans.