Serrated Polyposis Syndrome and Colorectal Cancer Risk

Serrated polyposis syndrome (SPS) is a clinical entity marked by the development of multiple serrated polyps throughout the colon and rectum and is recognised as the most common polyposis syndrome after familial adenomatous polyposis. The syndrome is defined by World Health Organization criteria, which encompass either a cumulative count of serrated lesions exceeding 20 or the presence of large (≥10 mm) proximal serrated polyps. SPS denotes a heightened risk of colorectal cancer (CRC), driven by the serrated neoplastic pathway in which sessile serrated lesions and traditional serrated adenomas evolve through aberrant BRAF or KRAS activation and widespread CpG island methylation. This epigenetic silencing frequently targets key mismatch repair genes, leading to microsatellite instability in a subset of tumours. Epidemiological estimates place lifetime CRC risk in SPS patients at up to 15–30 per cent without surveillance, although precise figures vary with polyp burden and histological subtype. Surveillance colonoscopy with systematic clearance of lesions is the cornerstone of management, aiming to intercept progression to advanced neoplasia. Emerging data support tailoring interval programmes according to individual risk stratification, balancing early detection against procedural burden. At a molecular level, germline variation in genes such as RNF43 and WNK2 has been implicated in a minority of cases, though penetrance appears variable. Global efforts now focus on refining endoscopic techniques, delineating genetic predisposition and integrating molecular biomarkers to optimise prevention and early intervention strategies in SPS.

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Serrated Polyposis Syndrome and Colorectal Cancer Risk publication trend

The graph below shows the total number of articles in serrated polyposis syndrome and colorectal cancer risk across all publications each year (not limited to Nature Index journals).

Technical terms

Serrated polyposis syndrome (SPS): A condition marked by numerous serrated colorectal polyps and elevated colorectal cancer risk.
Sessile serrated lesion (SSL): A flat or slightly elevated serrated polyp subtype prone to dysplasia and malignant transformation.
Traditional serrated adenoma (TSA): A serrated polyp with villiform architecture and cytological dysplasia.
CpG island methylator phenotype (CIMP): A molecular profile characterised by widespread promoter hypermethylation and gene silencing.
Microsatellite instability (MSI): A form of genetic hypermutability resulting from defective DNA mismatch repair.
Endoscopic submucosal dissection (ESD): A technique for en bloc resection of large or fibrotic colorectal lesions.
Advanced neoplasia: Colorectal lesions that are ≥10 mm, show high-grade dysplasia or have invasive features.

References

1. Personalised surveillance for serrated polyposis syndrome: results from a prospective 5-year international cohort study. Gut (2019).
2. Feasibility and Safety of Endoscopic Control for Patients with Serrated Polyposis Syndrome. Digestive Diseases (2023).
3. Long-Term Incidence of Advanced Colorectal Neoplasia in Patients with Serrated Polyposis Syndrome: Experience in a Single Academic Centre. Cancers (2021).
4. Germline pathogenic variants in RNF43 in patients with and without serrated polyposis syndrome. Familial Cancer (2024).
5. Germline mutations in WNK2 could be associated with serrated polyposis syndrome. Journal of Medical Genetics (2022).