Lynch Syndrome

Background

Lynch Syndrome (formerly known as hereditary non-polyposis colorectal cancer – HNPCC) is an autosomal dominant hereditary cancer syndrome, associated with a 40-80% [HEE] lifetime cancer risk.

The condition is caused by a germline defect in a DNA mismatch repair (MMR) gene. This results in failure to repair errors acquired during DNA replication, with the consequent accumulation of mutations leading to cancer. The increased cancer risk is not uniform across tumour types, but greatest in cancer of the bowel (colorectum), womb (endometrium) stomach, ovary, and other tissues.

People with LS have up to an 80% [BCUK] risk of developing colorectal cancer, and, in women, up to a 60% [Europe PMC] risk of developing endometrial cancer.

Lynch is estimated to affect roughly 1 in 400 [NHSE] people, translating to 175,000-250,000 individuals in the UK [BCUK] – however only 5% of these have been diagnosed. Consequently, many people with LS only discover they have the condition after they develop cancer.

Improving diagnosis of LS

Improving the diagnosis and management of LS will result in the earlier detection and prevention of cancer. Screening and risk-reducing strategies (such as daily aspirin) can prevent many LS associated cancers. A diagnosis of LS can also influence management plans for people who develop cancer. This includes informing the surgical approaches chosen and the use of specific immunotherapy and chemotherapy treatments.

The importance of detecting LS is reflected in NICE guidelines that include recommendations for:

universal screening for LS in people with colorectal and endometrial cancer
use of daily aspirin to reduce the risk of colorectal cancer in LS patients
recommendations for specific immunotherapy treatments for those with LS who develop metastatic colorectal or endometrial cancer

When adults are first diagnosed with colorectal or endometrial cancer, testing for mismatch repair proteins on tumours using immunohistochemistry (IHC) or testing for microsatellite instability (colorectal cancer only) can guide further testing to identify those in whom the cancer may have occurred because of LS. This includes testing for BRAF mutation in colorectal cancer, and MLH1 promoter methylation in both tumour types.

NHSE guidance for LS

NHS England has published a handbook for Cancer Alliances to support implementation of national LS pathways. This recommends that cancer MDTs take responsibility for initiating and completing LS testing pathways in cancer patients via mainstreaming (actioning of germline testing by the care team without requirement to see geneticist) and liaison with regional expert centres.

Genetic testing for LS is now commissioned at a national level through the NHS National Genomic Test Directory. Tests can be ordered by clinicians involved in patient management including oncologists, surgeons, and gastroenterologists if indicated.

LS and Genomics: National Transformation Project

The NHS GMSA National Lynch Syndrome project works to improve the identification and management of Lynch Syndrome. The project aims to align pathways and processes across the country to drive standardisation and equity of access to LS testing, with an initial focus on colorectal and endometrial cancer patients.

One important element of this is the appointment of dedicated ‘Lynch Champions’ at colorectal and gynaecological (endometrial) cancer MDTs, who will help deliver the transformation project locally. Every MDT ‘Lynch Champion’ needs to complete a short national training module. Other members of MDTs involved in patient care are encouraged to complete it too. In TVCA, Lynch Champions have been appointed in both colorectal and gynae cancer MDTs to be responsible for Lynch testing pathways across our geography.

NHSE guidance for colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (NHS BCSP) for patients with LS

In April 2023 NHSE confirmed:

“Symptomatic endoscopy providers should continue to deliver colonoscopic surveillance to all patients with a genetically confirmed diagnosis of Lynch Syndrome until they are notified in writing by an NHS BCSP provider that a patient is now receiving surveillance under the care of NHS BCSP. Only once symptomatic endoscopy providers have received written confirmation from an NHS BCSP provider, should they remove the named patient from their surveillance lists.
“If a patient with a genetically confirmed diagnosis of Lynch Syndrome makes an informed choice to withdraw from the NHS BCSP Lynch Syndrome surveillance programme, symptomatic endoscopy services will be notified in writing by an NHS BCSP provider to confirm this. In these circumstances symptomatic endoscopy providers should not remove the patient from their surveillance lists and should continue to invite them for their surveillance colonoscopies.”