Rates and outcomes of testing for lynch syndrome in a national colorectal cancer screening programme

ElsevierVolume 82, February 2023, 102314Cancer EpidemiologyAuthor links open overlay panelAbstractBackground

Lynch Syndrome (LS), the most common cause of hereditary colorectal cancer (CRC), is characterised by pathogenic variants in mismatch repair (MMR) genes. Universal testing of all CRCs for LS can increase detection. Rates and outcomes of testing in Ireland’s national CRC screening programme have not been examined previously.

Methods

CRCs diagnosed at two screening sites between 2015 and 2020 were identified. Patient records were used to determine if CRCs had been tested for MMR deficiency and if detected, what downstream testing to rule out LS or genetic testing to confirm LS was undertaken.

Results

Over five years, 206 CRCs were diagnosed. Testing for LS was carried out for 100% of CRCs at site A and 69% of CRCs at site B. Of CRCs tested for LS, 14 (8%) were MMR deficient. After downstream testing for BRAF mutation or hypermethylation of MLH1, three CRCs were identified as potentially LS-related. Of these two individuals declined genetic testing and one was lost to follow-up.

Conclusions

By 2020 both sites had implemented universal testing of all CRCs for LS. A small number of individuals were identified as being eligible for genetic testing for LS, however those offered declined testing and one individual was lost to follow up. This highlights the importance of universal testing and the need for referral pathways to ensure all appropriate individuals are referred onwards to genetic services.

Section snippetsBackground

Lynch Syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC), accounting for 2–4% of all CRC cases [1]. LS is an autosomal dominant condition arising from germline pathogenic mutations in mismatch repair (MMR) genes MLH1, MSH2, MSH6, PMS2 or an epigenetic mutation in the EPCAM gene which leads to silencing of MSH2.

Morbidity and mortality from CRC can be significantly reduced in those with LS through close endoscopic surveillance which aims to remove precursor lesions and

Methods

We performed a retrospective review of CRCs diagnosed through BowelScreen. The data was collected from two screening sites, the Mater Misericordiae University Hospital (MMUH) and St. Vincent’s University Hospital (SVUH) which are responsible for approximately 25% of screening activity nationally. Both institutions are dedicated cancer centres. All patients who underwent a colonoscopy through BowelScreen between January 2015 and December 2020 were included.

The BowelScreen electronic patient

Results

In total 5400 individuals had a colonoscopy through BowelScreen between January 2015 and January 2020. Of these 3478 individuals had a colonoscopy at site A and 1922 at site B. During the study period, 4% (n = 207) of the total study population were identified on the CORID system as having been assigned a diagnosis of “tumour”. 206 individuals had a histologically confirmed CRC. One individual who did not have a confirmed histological diagnosis of CRC was excluded. This individual was found to

Discussion

Universal testing of all newly diagnosed CRCs for LS has been shown to be cost-effective in identifying individuals with LS and has been endorsed internationally by a number of organisations including the National Institute for Health and Care Excellence (NICE) and the British Society of Gastroenterology (BSG) [3], [8]. In addition, identifying those with MMR deficient CRCs, with or without LS, is important as it has implications for therapeutic options such as the use of immune checkpoint

Conclusion

In conclusion, while universal testing for LS at the two BowelScreen screening sites was 89% overall, since 2020 all CRCs have been tested for LS. The prevalence of MMR deficiency was slightly lower than that seen in other population-based colorectal cancer screening cohorts which may relate to differing age profiles between the cohorts. While no individuals with LS were identified, 3 individuals with an indication for germline testing did not undergo testing and therefore the true prevalence

CRediT authorship contribution statement

Jane Cudmore: Conceptualization, Investigation, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. Lakshman Kumar, Neil O'Moráin: Data curation, Writing – review & editing, Garrett Cullen: Methodology, Writing – review & editing. Gareth Horgan: Methodology, Writing – review & editing. John Aird: Methodology, Writing – review & editing. Kieran Sheahan: Methodology, Writing – review & editing. Desmond C Winter: Methodology, Writing – review & editing. Rory

Funding

The authors received no specific funding for this work.

Declarations of interest

The authors declare no conflicts of interest.

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