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
. 2021 Apr;20(2):145-156.
doi: 10.1007/s10689-020-00206-0. Epub 2020 Sep 11.

Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas

George Kunnackal John  1   2 , Vipin Das Villgran  3 , Christine Caufield-Noll  4 , Francis Giardiello  5
Affiliations

Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas

George Kunnackal John et al. Fam Cancer. 2021 Apr.

Abstract

To perform a systematic assessment of universal Lynch syndrome (LS) screening yield in colorectal cancer (CRC) patients around the world. Universal screening for LS is recommended in all CRC patients. However, the variation in yield of LS screening in the setting of significant global variation in CRC prevalence is unknown. A systematic review of articles in the MEDLINE database was performed to identify studies performing universal screening for LS. All cases with microsatellite instability (MSI-H) or missing one or more proteins on immunohistochemistry (IHC) were considered screening positive. The overall pooled yield of universal LS screening in 97 study arms from 89 identified studies was 11.9% (5649/47545) and the overall pooled percentage of confirmed LS patients was 1.8% (682/37220). LS screening positivity varied significantly based on geographic region (Kruskal Wallis test, p < 0.001) and reported 5-year CRC prevalence in the country (Fisher's exact, p < 0.001). Significant inverse correlation was found between LS screening positivity and 5-year CRC prevalence (Pearson correlation, r = - 0.56, p < 0.001). The overall yield of LS screening was 15.00% (382/2553) and rate of confirmed LS was 7.7% (113/1475) in LS screening done in patients ≤ 50 years (16 studies). There is significant geographic variation in LS screening positivity with higher yield in countries with lower prevalence of CRC. Our results highlight the importance of universal LS screening in younger patients and low CRC prevalence countries.

Keywords: Lynch syndrome; Mismatch repair; Universal screening.

PubMed Disclaimer

References

    1. Lynch HT, Lynch PM, Lanspa SJ et al (2009) Review of the lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet 76:1–18 - PubMed - PMC
    1. Hampel H, Frankel WL, Martin E et al (2005) Screening for the lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352:1851–1860 - PubMed
    1. Chen S, Wang W, Lee S et al (2006) Prediction of germline mutations and cancer risk in the lynch syndrome. JAMA 296:1479–1487 - PubMed - PMC
    1. Aaltonen LA, Salovaara R, Kristo P et al (1998) Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 338:1481–1487 - PubMed
    1. Win AK, Jenkins MA, Dowty JG et al (2017) Prevalence and penetrance of major genes and polygenes for colorectal cancer. Cancer Epidemiol Biomark Prev 26:404–412

Publication types

MeSH terms

LinkOut - more resources