What studies evaluate the risk factors for Serrated Polyposis Syndrome (SPS)?

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Last updated: March 30, 2025View editorial policy

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From the Guidelines

The risk factors for serrated polyposis syndrome (SPS) include family history, with first-degree relatives of SPS patients showing an increased risk, as well as potential genetic links to mutations in genes like RNF43, although no single causative gene has been definitively established for most SPS cases. Several studies have evaluated these risk factors, focusing on both genetic and environmental contributors 1. The prevalence of SPS in the West is generally considered to be around 1:3000 in screening populations, and patients with SPS have an overall lifetime risk of CRC of approximately 7–70% 1. Key factors to consider in the risk assessment for SPS include:

  • Family history, with an increased risk in first-degree relatives of patients with SPS
  • Genetic mutations, such as RNF43, although the frequency of these pathogenic variants is too low to recommend routine testing
  • The presence of multiple serrated polyps, with a diagnosis of SPS made based on the revised WHO criteria, which include at least five serrated polyps proximal to the rectum, all >5 mm in size with at least two >10 mm in size, or at least 20 serrated polyps (of any size) with at least five located proximal to the rectum 1. Understanding these risk factors is crucial for identifying high-risk individuals who might benefit from earlier or more intensive screening protocols, such as yearly colonoscopic surveillance once the colon has been cleared of all lesions >5 mm in size, with the interval potentially extended to 2 yearly if no polyps ≥10 mm in size are identified at subsequent surveillance examinations 1.

From the Research

Risk Factors for Serrated Polyposis Syndrome

The following studies evaluate the risk factors for serrated polyposis syndrome:

  • A study published in 2019 2 found that first-degree relatives of individuals with serrated polyposis syndrome have a significant risk for colon cancer.
  • A 2022 study 3 identified epigenetic and environmental factors, especially smoking, as related to serrated polyposis syndrome.
  • Another study from 2021 4 associated the development of colorectal cancer with the occurrence of multiple serrated polyps throughout the colon and/or rectum.
  • A large multicentre study from 2016 5 found that patients with >2 sessile serrated adenomas/polyps proximal to splenic flexure and ≥1 proximal SSA/P with high-grade dysplasia were independent colorectal cancer risk factors.
  • A 2022 study 6 found that 20.5% of serrated polyposis syndrome patients tested were affected by heterozygous germline variants, including previously unreported associations with CHEK2 and POLD1.

Key Findings

Key findings from these studies include:

  • The importance of close endoscopic surveillance for individuals with serrated polyposis syndrome and their first-degree relatives 2, 5.
  • The need for genetic counseling and testing for individuals with serrated polyposis syndrome, especially those with a personal history of coexisting adenomatous polyposis or a concerning family history 2, 6.
  • The association between serrated polyposis syndrome and an increased risk of colorectal cancer, especially in individuals with specific polyp features such as sessile serrated adenomas/polyps proximal to splenic flexure and high-grade dysplasia 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hereditary or Not? Understanding Serrated Polyposis Syndrome.

Current treatment options in gastroenterology, 2019

Research

Serrated polyposis syndrome; epidemiology and management.

Best practice & research. Clinical gastroenterology, 2022

Research

Germline variant testing in serrated polyposis syndrome.

Journal of gastroenterology and hepatology, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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