Lynch Syndrome (DRAFT)

Overview

Lynch syndrome (LS) is an inherited autosomal dominant mismatch repair (MMR) deficiency that affects around 1 in 450 people in the United Kingdom. However, only 1 in 20 people (5%) with LS know they have it.

LS is recognised to be driver of around 3.5% of colorectal and endometrial cancers. It also increases the risk of other ‘Lynch-related’ epithelial derived cancers (epithelial ovarian cancer, ureteric cancer, transitional cell cancer of renal pelvis).

The lifetime risk of developing any cancer is dependent on which underlying MMR gene pathogenic variant is affected and can be as high as 75% for females and 58% for males. The prevalence of cancer in the adult LS population is between 4-5% which is higher than the Urgent Suspected Cancer referral threshold of 3% in the symptomatic general population.

Who to refer

Referrals to determine if a patient has lynch syndrome from primary care either relate to the patient having a known relative with lynch syndrome (the patient may or may not have a cascade testing letter as a result of their relatives' positive test) or a patient/clinician may be concerned about a family history of cancer.

From primary care, patients can be referred to the Bristol Regional Genetics Service if they meet the following criteria.

R210 panel criteria 4: Clinical Criteria for germline testing in an unaffected individual

1. First degree relative (FDR) affected with Lynch-related cancer (see footnote), AND
2. Family history of colorectal cancer/Lynch-related cancers reaches Amsterdam Criteria (≥3 cases over ≥2 generations with ≥1 case affected <50 years) AND
3. Tumour sample analysis from affected family member has been attempted and is not possible, failed, indeterminate or indicates MMR deficiency (via IHC or MSI), AND
4. Somatic sequencing is not possible, or failed, AND
5. No living affected individual is available for genetic testing

i.e. a patient without cancer can be referred for testing if they have a FDR with a lynch-related cancer with an Amsterdam criteria family history of lynch related cancer, and testing is not possible, for whatever reason, on the original family member tumour sample.

Red Flags

As patients with confirmed lynch syndrome have an increased risk of developing several different types of cancer, clinicians should be alert to any red flag symptoms and refer patients for further investigation as indicated.

Referral

GPs should make routine referrals to the Clinical Genetics Service through the eRS system.

Where applicable, and to provide accurate advice for your patient, please provide details of any relatives affected with a genetic condition, including their names.

Patients referred with a personal and/or family history of cancer will be triaged for one of the following:

• A family history questionnaire will be sent to the patient to gather more information and confirm cancer diagnoses in the family to inform risk assessment.
• The patient will be added to our waiting list for an appointment with a genetic counsellor or consultant.
• If the patient is deemed not to be at significantly increased risk of cancer, a letter will be written to the referring clinician and they will not be offered an appointment.

If genetic testing has already taken place in the family, please provide details of any relevant relatives, including their names.

For unaffected individuals, genetic testing for cancer usually requires the identification of a genetic change in an affected family member, so it may be more appropriate for an affected family member to be seen and assessed first by their local genetics department.

Following diagnosis

Patients with Lynch Syndrome can manage and reduce their risk through:

• Taking aspirin - NICE guidance (NG151) recommends people with Lynch syndrome consider taking aspirin daily for more than 2 years to prevent colorectal cancer. BNSSG ICS and the GMSA have agreed local guidance to support this Aspirin treatment 
• Losing weight - the risk of early onset colorectal cancer is more than doubled in Lynch syndrome patients who are also obese (Mathers et al)
• Stopping smoking - people with Lynch syndrome may be at increased risk of colorectal cancer if they smoke regularly (Pande et al)
• Dietary advice - The CAPP2 study tested a daily supplement of resistant starch, also known as fermentable fibre in people with Lynch syndrome. This has shown a highly significant reduction over ten years in cancers in other part of the body such as the stomach, liver and pancreas. (Mathers et al in press).
• Surgery - Patients diagnosed with Lynch syndrome may choose to have adaptive surgery (bowel resection, hysterectomy or oophorectomy) to reduce their risk of developing cancer.
• Surveillance pathways to support early detection - there is guidance on recommended surveillance pathways for people with Lynch syndrome highlighted in this handbook B0622-Implementing-Lynch-syndrome-testing-and-surveillance-pathways-version-1.2.pdf  Surveillance colonoscopy every two years from age 25 if MLH1 and MSH2 and from age 35 if MSH6 or PMS2 germline mutations (now administered by Bowel Cancer Screening Programme who receive referral directly from clinical genetics after diagnosis)
• Cascade testing of family members (carried out by clinical genetics after diagnosis)
• Referral to gynaecology (carried out by clinical genetics after diagnosis)

Resources

B0622-Implementing-Lynch-syndrome-testing-and-surveillance-pathways-version-1.2.pdf

Lynch Syndrome UK website. https://www.lynch-syndrome-uk.org/projects-2

National Genomics Education Programme – GeNotes https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/lynch-syndrome/#inheritance-and-genomic-counselling

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