Research shows that there could be over 175,000 people in the UK with the genetic condition Lynch syndrome (National Institute for Health and Care [NICE], 2016). As healthcare professionals, it is vital to follow the evidence to determine who may be affected by Lynch syndrome in order that they can have appropriate screening to decrease their risk of bowel cancer and other related cancers. Those leads are largely found in two ways. First, through testing those with bowel cancer to see if they have Lynch syndrome so that their relatives can be tested to see if they have also inherited the condition, this is done in secondary care. The second way is through identifying individuals with what are termed ‘high risk’ family histories so that they can be tested for Lynch syndrome. This can be achieved in primary or secondary care.  

WHAT IS LYNCH SYNDROME?  

Lynch syndrome is an inherited genetic condition. It is caused by a germline pathogenic variant in one of four DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2. Pathogenic variant in another non-MMR gene, known as EPCAM, can also cause Lynch syndrome (NHS England, 2021). MMR genes encode proteins and are involved in recognising and repairing errors in DNA sequence, which occur when DNA is replicated during cell division. Variants in MMR genes can lead to failure to repair DNA errors. A child who has a parent with a pathogenic variant has a 50% chance of inheriting that variant. About half of all people with Lynch syndrome develop colorectal cancer (NHS England, 2021). It is also responsible for other cancers, including endometrial, gastric, small bowel, urothelial and brain cancers. Lynch syndrome is estimated to cause over 1,100 cases of bowel cancer in the UK, with many of them occurring in those under the age of 50 (NHS England, 2021).  

NICE GUIDANCE FOR DETECTION OF LYNCH SYNDROME  

Since 2017, NICE has recommended that all people diagnosed with colorectal cancer are tested for Lynch syndrome using immunohistochemistry or microsatellite instability testing (NICE, 2017). In October 2020, NICE also recommended that all people diagnosed with endometrial cancer are tested for Lynch syndrome using immunohistochemistry.  

The Lynch syndrome pathway can be split into four stages (NHS England, 2021): 

• Stage 1: Initial tumour testing:  
  1. Biopsy taken, and cancer diagnosed  
  2. Test tumour using immunohistochemistry or microsatellite instability  
• Stage 2: Germline testing:  
  3. Test suggests cancer could be caused by Lynch syndrome  
  4. If not already done, consent to perform germline testing  
  5. Perform germline testing  
• Stage 3: Management of index:  
  6. If Lynch syndrome is confirmed, communicate results to patient and refer to genetics service 
  7. Agree a screening and management plan and refer to relevant services  
• Stage 4: Cascade testing:  
  8. Cascade testing of at-risk family members.  

At present, the number of patients being tested for Lynch syndrome at point of colorectal cancer diagnosis varies greatly from trust to trust (NHS England, 2021). Cancer alliances across the UK have put in place plans to improve this.  

WHY IS TESTING FOR LYNCH SYNDROME SO IMPORTANT?  

It is important that people with Lynch syndrome have regular colonoscopies. This can reduce the risk of cancer by removing polyps before they can change from adenomas (benign polyps) to cancers. Colorectal cancers occur in people with Lynch syndrome by developing through an accelerated adenoma to carcinoma sequence (Edwards and Monahan, 2022). 

A colonoscopy is a test that looks inside the bowel for cancer and polyps. If detected early enough, polyps can be removed at the time of the colonoscopy so that they never get the chance to progress into cancers. UK guidelines for those with proven Lynch syndrome recommend colonoscopy surveillance every two years (Edwards and Monahan, 2022). Following a clinical consensus meeting facilitated by Bowel Cancer UK, there is now a move for the national bowel cancer screening programme to deliver the Lynch surveillance programme so that patients can receive the same high quality screening programme as the eligible asymptomatic population (Bowel Cancer UK, 2022). In addition to surveillance, there is now good evidence that the taking of aspirin in those with Lynch syndrome significantly reduces incidence of colorectal cancer (Edwards and Monahan, 2022). NICE introduced this recommendation in 2020, with the caution that this should be following clinical consultation (NICE, 2020).  
 

HOW CAN WE HELP WHEN WORKING IN PRIMARY AND SECONDARY CARE?  

Identifying those that may have Lynch syndrome but are unaware and therefore not benefitting from surveillance can genuinely save lives. So, when talking to patients it is important to take the opportunity to ask about family history. There are some red flags to remember — the easiest way is through the three, two, one rule. Are there three affected relatives with bowel cancer or Lynch associated cancers, across two generations, with at least one person affected under the age of fifty? (Muller et al, 2019). 

If you identify a family history such as that described by the three, two, one rule, it is vital that the patient, should they agree, be referred to a local genetics service or family history clinic so that genetic testing and appropriate surveillance can be arranged.  

The importance of identifying those affected by Lynch syndrome for those working in both primary and secondary care in order to save lives cannot be underestimated. What is clear though is that the availability of guidance and pathways described above, and the tireless work of healthcare professionals involved provide a clear opportunity for those working in primary and secondary care to make a difference.