SP6.10 Is 3% prevalence of Lynch Syndrome an overestimation?

Abstract Introduction The National Lynch Syndrome Project (NLSP) reports that Lynch syndrome (LS) is estimated to account for 3% of colorectal cancers (CRC), and that less than 5 % of LS patients are aware of having LS, and so recommended all new CRCs are tested for LS. Methods The NLSP was implemented at a hospital in Southwest England. All tumours were tested for microsatellite instability (MSI), and if positive, subsequently for BRAF mutation and MLH1 methylation. If these indicated the possibility of LS, the patient was referred to Clinical Genetics for testing of germline non-tumour cells for LS. Results 346 new CRCs were diagnosed from April 2023 to September 2024. MSI, BRAF and MLH1 testing revealed 14 patients (4.1%) to have unmethylated MLH 1. Only one of these patients was found to have LS; another was diagnosed by having a germline hypermethylation mutation. Two were already known to have LS. 4 from 346 patients tested gives a prevalence of 1.2%. 2 patients are still awaiting testing; even if these 2 patients both have LS the prevalence would only be 1.7%. The largest international meta-analysis of LS found the prevalence of LS in CRC to be 2.2% (95% CI 1.8-2.5%). Discussion The incidence of the new LS patients in our population is significantly lower than expected. The reason for this very low prevalence is unknown at present; as the NLSP makes new very large datasets available, it may become clear that the previous estimate of LS prevalence is too high.