Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jul 18;15(14):3663.
doi: 10.3390/cancers15143663.

The Prevalence and Molecular Landscape of Lynch Syndrome in the Affected and General Population

Laura Roht  1   2 , Piret Laidre  2 , Mikk Tooming  1   3 , Neeme Tõnisson  2   4 , Margit Nõukas  4   5 , Miriam Nurm  4 , Estonian Biobank Research Team  4 , Hanno Roomere  3 , Kadri Rekker  3 , Kadri Toome  3 , Olga Fjodorova  3 , Ülle Murumets  3 , Ustina Šamarina  3 , Sander Pajusalu  1   2   3 , Anu Aaspõllu  6 , Liis Salumäe  7 , Kristina Muhu  8 , Jaan Soplepmann  9   10 , Katrin Õunap  1   2 , Tiina Kahre  1   3
Affiliations
Review

The Prevalence and Molecular Landscape of Lynch Syndrome in the Affected and General Population

Laura Roht et al. Cancers (Basel). .

Abstract

Background: Lynch syndrome (LS) is the most frequent genetically pre-disposed colorectal cancer (CRC) syndrome, accounting for 2-3% of all CRC cases. In Estonia, ~1000 new cases are diagnosed each year. This retroactive and prospective study aimed to estimate the prevalence of LS and describe disease-causing variants in mismatch repair (MMR) genes in a diagnostic setting and in the Estonian general population.

Methods: LS data for the diagnostic cohort were gathered from 2012 to 2022 and data for the general population were acquired from the Estonian Biobank (EstBB). Furthermore, we conducted a pilot study to estimate the improvement of LS diagnostic yield by raising the age limit to >50 years for immunohistochemistry analysis of MMR genes.

Results: We estimated LS live birth prevalence between 1930 and 2003 in Estonia at 1:8638 (95% CI: 1: 9859-7588). During the study period, we gathered 181 LS individuals. We saw almost a six-fold increase in case prevalence, probably deriving from better health awareness, improved diagnostic possibilities and the implementation of MMR IHC testing in a broader age group.

Conclusion: The most common genes affected in the diagnostic and EstBB cohorts were MLH1 and PMS2 genes, respectively. The LS diagnosis mean age was 44.8 years for index cases and 36.8 years (p = 0.003) for family members. In the MMR IHC pilot study, 29% had LS.

Keywords: Lynch syndrome; cancer genetics; immunohistochemistry (IHC); mismatch repair (MMR) genes.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Lynch syndrome’s birth prevalence (cases per 100,000 live births) in the diagnostic and EstBB cohorts during the years 1930–2020 in Estonia. Confidence interval (95% CI) is shown in accented lines.
Figure 2
Figure 2
Lynch syndrome’s prevalence (cases per 100,000 persons) in Estonia from 2012 to 2022. Confidence interval (95% CI) is shown in accented lines.
Figure 3
Figure 3
(A) Mean and median age of LS diagnosis in the diagnostic cohort. (B) Mean and median age of first tumor diagnosis in the diagnostic cohort.
Figure 4
Figure 4
Cancer cases in health history in diagnostic cohort’s index cases (A) vs. family members (B).
Figure 5
Figure 5
Pedigree of the case report.
Figure 6
Figure 6
MMR IHC pilot study groups.
See this image and copyright information in PMC

References

    1. Kim J.C., Bodmer W.F. Genomic landscape of colorectal carcinogenesis. J. Cancer Res. Clin. Oncol. 2022;148:533–545. doi: 10.1007/s00432-021-03888-w. - DOI - PMC - PubMed
    1. Abu-Ghazaleh N., Kaushik V., Gorelik A., Jenkins M., Macrae F. Worldwide prevalence of Lynch syndrome in patients with colorectal cancer: Systematic review and meta-analysis. Genet. Med. 2022;24:971–985. doi: 10.1016/j.gim.2022.01.014. - DOI - PubMed
    1. Lynch H.T., Snyder C.L., Shaw T.G., Heinen C.D., Hitchins M.P. Milestones of Lynch syndrome: 1895-2015. Nat. Rev. Cancer. 2015;15:181–194. doi: 10.1038/nrc3878. - DOI - PubMed
    1. Biller L.H., Syngal S., Yurgelun M.B. Recent advances in Lynch syndrome. Fam. Cancer. 2019;18:211–219. doi: 10.1007/s10689-018-00117-1. - DOI - PMC - PubMed
    1. Biller L.H., Horiguchi M., Uno H., Ukaegbu C., Syngal S., Yurgelun M.B. Familial Burden and Other Clinical Factors Associated with Various Types of Cancer in Individuals With Lynch Syndrome. Gastroenterology. 2021;161:143–150 e144. doi: 10.1053/j.gastro.2021.03.039. - DOI - PMC - PubMed

LinkOut - more resources