Presentation: Patient with a genetic diagnosis of Lynch syndrome
Lynch syndrome is an inherited colorectal cancer condition that confers a high risk of developing other cancers. It is essential to identify the causative gene variant before making management recommendations.
At a glance:
- Lynch syndrome (formerly known as hereditary non-polyposis colorectal cancer) is inherited in an autosomal dominant pattern, meaning that first-degree relatives of an affected individual have a 50% chance of also carrying a familial variant.
- Individuals with Lynch syndrome are at high risk of developing a range of cancers (including, most commonly, colorectal and endometrial, as well as ovarian, stomach and others).
- Patients with Lynch syndrome can be offered personalised risk management, which includes surveillance, risk-reducing surgery, screening for helicobacter pylori and the use of aspirin for chemoprophylaxis.
- Alert! The lifetime risk of associated cancers can vary significantly depending on the causative gene; there are 4 different genes which are associated with Lynch syndrome. It is important to ascertain this prior to making management recommendations.
Example clinical scenario
One of your patients, a 46-year-old woman, has been diagnosed with colorectal cancer. Subsequent tumour testing following NICE guidance suggested Lynch syndrome, and she was referred to clinical genetics services for germline genomic testing. She recently received results showing that she has a pathogenic variant in one of the genes known to cause Lynch syndrome. She attends your practice with a letter from clinical genetics that recommends starting aspirin and being tested for helicobacter pylori infection.
Identifying those at risk of a genetic condition
Lynch syndrome should be suspected if:
- cancer presents at a young age (below 50);
- synchronous or metachronous cancer is present (multiple cancers at once);
- there is a clustering of there are Lynch-associated cancers in the family for instance bowel, endometrial, ovarian, upper gastrointestinal (such as gastric, duodenal, pancreatic or bile duct) or genitourinary cancer (such as bladder, ureter or kidney) ; and
- there is a family history of Lynch syndrome and/or a known familial pathogenic variant.
Those with specific pathogenic variants do not all carry the same risk of a specific cancer. There are published UK management recommendations for Lynch syndrome, including gene-specific guidelines that show cancer risks according to sex.
What should you do next?
- Ensure that there is a code for Lynch syndrome entered into the primary care record and include the gene affected in free text. The purpose of this is to flag that the patient is at high risk of other cancers, and that primary care should have a low threshold for urgent investigation under suspected cancer referral pathways.
- Refer, if the patient hasn’t already been referred, to clinical genetics services, who will arrange onward referral for bowel screening and registration with the England National Lynch Syndrome Registry.
- Offer the use of aspirin to reduce the risk of bowel cancer using the decision aid tool from NICE.
- Screen (one-off) and treat for helicobacter pylori. This can reduce stomach cancer risk by 50%.
- Refer to gynaecology for discussion of risk-reducing surgery at the appropriate age. This should be detailed within communication from clinical genetics services and will vary according to the gene affected.
- Men may have an increased risk of prostate cancer; any recommendations for prostate-specific antigen (PSA) testing should be detailed within communication from clinical genetics services.
- Emphasise to your patient the importance of having a low threshold for seeking healthcare review, even with vague symptoms, due to the high risk of other cancers.
- Discuss generic risk reduction with your patient, such as a healthy lifestyle and diet, maintaining a healthy BMI and the avoidance of smoking and excess alcohol consumption.
- Offer referral to discuss preimplantation genetic testing and other reproductive options.
- Ensure (re-refer if necessary) that your patient has had contact with local clinical genetics service for support and wider family testing.
- For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
- Information about patient eligibility and test indications were correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.
Resources
For clinicians
- NHS England’s Genomics Education Programme: New Lynch syndrome registry ‘game-changing’ for patients
- RM Partners West London Cancer Alliance: Lynch syndrome online training for primary care clinicians
References:
- Huntley C, Loong L, Mallinson C and others. ‘The comprehensive English National Lynch Syndrome Registry: development and description of a new genomics data resource‘. eClinicalMedicine (2024): volume 69, article number 102,465. DOI: 10.1016/j.eclinm.2024.102465
For patients
- NICE: Lynch syndrome: Should I take aspirin to reduce my chance of getting bowel cancer? (PDF, three pages)
- Lynch Syndrome UK
- Macmillan Cancer Support: Lynch syndrome
- Royal Marsden NHS Foundation Trust: A beginner’s guide to Lynch syndrome (PDF, 64 pages)