Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system

Abstract

Purpose Referrals for Lynch syndrome (LS) assessment have traditionally been based on personal and family medical history. The introduction of universal screening practices has allowed for referrals based on immunohistochemistry tests for mismatch repair (MMR) protein expression. This study aims to characterize the effect of universal screening in a publicly funded healthcare system with comparison to patients referred by traditional criteria, from January 2012 to March 2017. Methods Patient files from the time of initiation of universal screening from 2012 to 2017 were reviewed. Patients were sorted into two groups: (a) universally screened and (b) referred by traditional methods. Mutation detection rates, analysis of traditional testing criteria met, and cascade carrier testing were evaluated. Results The mutation detection rate of the universal screening group was higher than the traditionally referred group (45/228 (19.7%) vs 50/390 (12.5%), P = .05), though each were able to identify unique patients. An analysis of testing criteria met by each patient showed that half of referred patients from the universal screening group could not meet any traditional testing criteria. Conclusion The implementation of universal screening in a publicly funded system will increase efficiency in detecting patients with LS. The resources available for genetic testing and counseling may be more limited in public systems, thus inclusion of secondary screening with BRAF and MLH1 promoter hypermethylation testing is key to further optimizing efficiency.

Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort

“…Our observed MMR mutation prevalence falls within the published range of 2–6% amongst unselected ECs [ 2 , 3 , 4 , 5 , 6 ] but is nonetheless at the higher end of the range compared to most universal screening studies employing either MSI and/or IHC [ 4 , 27 , 37 , 38 ]. This could be due to differences in the types of PVs identified by MSI vs. IHC, a higher-than-average rate of LS among our study cohort (the MUHC is a university teaching hospital, perhaps serving a higher-risk population), an increase in the number of individuals missed by other two-step screening protocols (MSI then IHC, or IHC then MSI), differences in IHC efficacy between centers, or the fact that 16 out of 17 patients referred for genetic counselling in our study ultimately consented to genetic testing, as compared to higher rates of drop-out/decline of testing in other published studies [ 29 , 37 , 38 ].…”

“…Recently, Lee et al evaluated the efficiency of IHC screening for LS in a Vancouver population, and found that the implementation of universal screening increased efficiency in detecting LS. They suggested that secondary screening, including BRAF and MLH1 promoter hypermethylation testing, could further increase cost-effectiveness in a universal healthcare system [ 29 ]. Our goal was to therefore contribute to the existing literature regarding the feasibility and performance of a universal IHC screening program for all newly diagnosed ECs within a single Canadian university hospital setting.…”

A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals

“…Universal MMR screening programs have been demonstrated to increase detection of Lynch syndrome although outcome and efficiency is influenced by age groups including screening strategy, completeness of analyses and successful prevention of CRC-related mortality in individuals at increased risk [ 9 , 10 , [22] , [23] , [24] ]. Clinical implementation, however, varies between countries and institutions and is sometimes restricted e.g.…”

Parent-of-origin detection and chromosome-scale haplotyping using long-read DNA methylation sequencing and Strand-seq

“…In the absence of PofO information due to parents being unavailable, deceased, or declining genetic testing, cascade genetic testing must be offered to both sides of the family until segregation is confirmed. This may be costly and burdensome to patients and families, exacerbating already low rates of uptake of cascade genetic testing 19,20 . Eliminating the need to test one side of the family is a clear benefit and a major clinical utility of defining PofO for pathogenic variants, and more broadly, establishing chromosome-length haplotypes with accurate parental segregation of genomic variation has widespread applications.…”