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
. 2025 Sep 26;16(11):e00923.
doi: 10.14309/ctg.0000000000000923. Online ahead of print.

Low Yield of Genetic Testing in Serrated Polyposis Syndrome

Ira Upadhye  1 , Husam Al Maliki  1   2 , Victoria Cuthill  3 , Andrew Latchford  1   3 , Kevin Monahan  1   3
Affiliations

Low Yield of Genetic Testing in Serrated Polyposis Syndrome

Ira Upadhye et al. Clin Transl Gastroenterol. .

Abstract

Introduction: Serrated polyposis syndrome (SPS) is clinically defined by the presence of multiple serrated polyps in the colon and rectum, and is associated with increased colorectal cancer risk. SPS is the most prevalent polyposis condition; however, its genetic basis remains poorly characterized. The British Society of Gastroenterology recommends gene panel testing for all patients with SPS to rule out other polyposis conditions. The aim of this study was to evaluate the diagnostic yield of genetic testing in patients with SPS.

Methods: We conducted a retrospective, cross-sectional analysis using the Polyposis Registry from St. Mark's Hospital, London, a national referral center in the United Kingdom. Patients with SPS who underwent genetic testing between April 4, 2009 and February 9, 2024, and met the SPS WHO criteria were included. Genetic variants were identified from test reports, and clinical data were extracted from medical records.

Results: In total, 573 people with SPS were identified in our registry, of whom 258 underwent genetic testing. Of these, 119 underwent target gene testing and 139 underwent multigene panel testing. No pathogenic variants were detected through targeted genetic testing. On multigene panel testing, pathogenic germline variants were found in 4 patients (2.9%), including 3 with Lynch syndrome (2 with PMS2 , one with MSH2 ) and one with an RNF43 variant.

Discussion: Genetic testing demonstrated a low diagnostic yield in this SPS cohort, suggesting undefined genetic risk or involvement of other pathophysiological factors. Therefore, genetic testing seems to have limited utility in patients with SPS and may primarily identify those with an incidental diagnosis of Lynch syndrome.

Keywords: colorectal cancer; serrated polyposis syndrome; serrated polyps.

PubMed Disclaimer

Conflict of interest statement

Guarantor of the article: Kevin Monahan, PhD.

Specific author contributions: V.C., and K.M.: study design and methodology. I.U.: data collection. I.U., and K.M.: analysis. I.U., H.A., A.L., and K.M.: interpretation of the results. I.U., H.A., and K.M: drafting the manuscript. All authors: reviewing, editing the manuscript and approving the final draft.

Financial support: None to report.

Potential competing interests: None to report.

Figures

Figure 1.
Figure 1.
Flowchart of patients included and excluded in the study. SPS, serrated polyposis syndrome.
Figure 2.
Figure 2.
Flowchart showing the outcome of genetic testing in serrated polyposis syndrome cohort. VUS, variant of unknown significance.
See this image and copyright information in PMC

References

    1. Fousekis FS, Mitselos IV, Christodoulou DK. Diagnosis, epidemiology and management of serrated polyposis syndrome: A comprehensive review of the literature. Am J Transl Res 2021;13(6):5786–95. - PMC - PubMed
    1. Monahan KJ, Bradshaw N, Dolwani S, et al. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020;69(3):411–44. - PMC - PubMed
    1. Crockett SD, Nagtegaal ID. Terminology, molecular features, epidemiology, and management of serrated colorectal neoplasia. Gastroenterology 2019;157(4):949–66.e4. - PubMed
    1. Kupfer SS, Burke CA. Patients in whom to consider genetic evaluation and testing for hereditary colorectal cancer syndromes. Am J Gastroenterol 2020;115(1):1–4. - PMC - PubMed
    1. Yan HHN, Lai JCW, Ho SL, et al. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation. Gut 2017;66(9):1645–56. - PubMed

LinkOut - more resources