Colorectal cancer genetic variants are also associated with serrated polyposis syndrome susceptibility

J Med Genet. 2020 Oct;57(10):677-682. doi: 10.1136/jmedgenet-2019-106374. Epub 2020 Mar 13.


Background: Serrated polyposis syndrome (SPS) is a clinical entity characterised by large and/ormultiple serrated polyps throughout the colon and increased risk for colorectal cancer (CRC). The basis for SPS genetic predisposition is largely unknown. Common, low-penetrance genetic variants have been consistently associated with CRC susceptibility, however, their role in SPS genetic predisposition has not been yet explored.

Objective: The aim of this study was to evaluate if common, low-penetrance genetic variants for CRC risk are also implicated in SPS genetic susceptibility.

Methods: A case-control study was performed in 219 SPS patients and 548 asymptomatic controls analysing 65 CRC susceptibility variants. A risk prediction model for SPS predisposition was developed.

Results: Statistically significant associations with SPS were found for seven genetic variants (rs4779584-GREM1, rs16892766-EIF3H, rs3217810-CCND2, rs992157-PNKD1/TMBIM1, rs704017-ZMIZ1, rs11196172-TCF7L2, rs6061231-LAMA5). The GREM1 risk allele was remarkably over-represented in SPS cases compared with controls (OR=1.573, 1.21-2.04, p value=0.0006). A fourfold increase in SPS risk was observed when comparing subjects within the highest decile of variants (≥65) with those in the first decile (≤50).

Conclusions: Genetic variants for CRC risk are also involved in SPS susceptibility, being the most relevant ones rs4779584-GREM1, rs16892766-EIF3H and rs3217810-CCND2.

Keywords: colorectal cancer; genetic association study; genetic predisposition to disease; low-penetrance genetic variant; serrated polyposis syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / complications
  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology
  • Aged
  • Colon / pathology
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cyclin D2 / genetics
  • Eukaryotic Initiation Factor-3 / genetics
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Polyps / genetics
  • Polyps / pathology
  • Transcription Factor 7-Like 2 Protein / genetics
  • Transcription Factors / genetics


  • CCND2 protein, human
  • Cyclin D2
  • Eukaryotic Initiation Factor-3
  • GREM1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • ZMIZ1 protein, human
  • EIF3I protein, human