Presentation: Patient with a relative who has a Lynch syndrome-associated variant

A 27-year-old woman attends clinic worried that she may have inherited a ‘cancer gene’, after her father was diagnosed with bowel cancer. She mentions that her father underwent genomic testing and was found to have a gene change resulting in a diagnosis of Lynch syndrome.

• Lynch syndrome is inherited in an autosomal dominant pattern, meaning that children of individuals with a Lynch syndrome-associated constitutional (germline) variant have a 50% chance of inheriting the same variant.
• It is important to ascertain how your patient is related to the person who has the pathogenic variant. This will help confirm their likelihood of having inherited that variant.

• Patients at risk of having inherited the variant should be offered referral to their local clinical genetics service, which will provide access to information and counselling about testing.
  • Include details of the affected family member in your referral to clinical genetics (for example, name and date of birth) so that the team can obtain the consent, reports and samples needed to proceed with testing should the patient wish.
  • Including the relative’s details in a referral letter does not break confidentiality because the information has come from the patient, who is a third party.
• Upon referral, the clinical genetics team will ascertain which is the most appropriate family member to be tested. Testing of first-degree relatives in secondary care (including adult children, siblings and parents) will usually be offered sequentially to identify which family members are likely to be carrying the familial gene variant and therefore the cancer-predisposing syndrome. Testing may be offered to more distant relatives if intervening relatives are unavailable (for example, being deceased or living outside of the UK).
• If a person carries a pathogenic variant that increases their chance of having a cancer predisposition syndrome, clinical management may include additional screening, risk-reducing measures (for example, lifestyle advice, medication and/or surgical intervention) and symptom vigilance.
  • The lifetime chance of Lynch syndrome-associated cancers (most commonly colorectal cancer and endometrial cancer, as well as ovarian, pancreaticobiliary, gastric, small intestinal, brain, urinary tract, skin and other cancers) can vary significantly depending on the causative gene variant, with different guidelines in place accordingly.
• Individuals with a relative known to carry a pathogenic Lynch syndrome-associated variant may be eligible for additional screening recommendations, even if they do not wish to pursue predictive testing.
• Predictive testing can generate feelings of despair or anxiety in those who have inherited the familial variant, and guilt in those who have not. Your patient may need additional support, regardless of the result.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

For clinicians

• National Genomic Test Directory
• RM Partners West London Cancer Alliance: Lynch syndrome online training for primary care clinicians
• UK Cancer Genetics Group: UKCGG leaflets and guidelines (see ‘Lynch syndrome’)

For patients

• Cancer Research UK: Family history and inherited cancer genes
• Macmillan Cancer Support: Family history, genes and cancer risk
• Macmillan Cancer Support: Lynch syndrome
• Royal Marsden NHS Foundation Trust: A beginner’s guide to Lynch syndrome (PDF, 64 pages)