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Colorectal cancer genetic variants are also associated with serrated polyposis syndrome susceptibility
  1. Coral Arnau-Collell1,
  2. Yasmin Soares de Lima1,
  3. Marcos Díaz-Gay1,
  4. Jenifer Muñoz1,
  5. Sabela Carballal1,
  6. Laia Bonjoch1,
  7. Leticia Moreira1,
  8. Juan José Lozano2,
  9. Teresa Ocaña1,
  10. Miriam Cuatrecasas3,
  11. Aranzazu Díaz de Bustamante4,
  12. Antoni Castells1,
  13. Gabriel Capellà5,
  14. Luis Bujanda6,
  15. Joaquin Cubiella7,
  16. Daniel Rodríguez-Alcalde8,
  17. Francesc Balaguer1,
  18. Clara Ruiz-Ponte9,
  19. Laura Valle5,
  20. Victor Moreno10,
  21. Sergi Castellvi-Bel1
  1. 1Gastroenterology Department, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Barcelona, Spain
  2. 2Bioinformatics Platform, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
  3. 3Pathology Department, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) and Tumor Bank-Biobank, Hospital Clínic, Barcelona, Spain
  4. 4Genetics Unit, Hospital Universitario de Mostoles, Mostoles, Spain
  5. 5Hereditary Cancer Program, Catalan Institute of Oncology, Oncobell, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Barcelona, Spain
  6. 6Gastroenterology Department, Hospital Donostia-Instituto Biodonostia, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Basque Country University (UPV/EHU), San Sebastian, Spain
  7. 7Gastroenterology Department, Complexo Hospitalario Universitario de Ourense, Instituto de Investigación Sanitaria Galicia Sur, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Ourense, Spain
  8. 8Digestive Disease Section, Hospital Universitario de Mostoles, Mostoles, Spain
  9. 9Fundación Pública Galega de Medicina Xenómica, Grupo de Medicina Xenómica_USC, Instituto de Investigación Sanitaria de Santiago (IDIS), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain
  10. 10Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO); Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL); Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
  1. Correspondence to Dr Sergi Castellvi-Bel, Genetic predisposition to gastrointestinal cancer Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 153, 08036 Barcelona, Spain; sbel{at}


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.

  • serrated polyposis syndrome
  • colorectal cancer
  • genetic association study
  • low-penetrance genetic variant
  • genetic predisposition to disease

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  • Correction notice This article has been corrected since it was published Online First. The name of author Miriam Cuatrecasas has been corrected.

  • Contributors CA-C, VM and SC-B planned the study. CA-C, YSdL, MD-G, JM, SC, LB, LM, JJL, TO, MC and SC-B conducted the study. CA-C, YSdL, MD-G, JM, SC, LB, LM, JJL, TO, MC, ADdB, LB, JC, DR-A, FB, CR-P, LV, VM and SC-B collected data. CA-C, YSdL, AC, GC, VM and SC-B interpreted data. CA-C and SC-B drafted the manuscript. The final draft of the manuscript was approved by all authors.

  • Funding CA-C, JM and JJL were supported by a contract from CIBEREHD. YSdL was supported by a fellowship (LCF/BQ/DI18/11660058) from 'la Caixa' Foundation (ID 100010434) funded EU Horizon 2020 Programme (Marie Skłodowska-Curie grant agreement no. 713673). LB was supported by a Juan de la Cierva postdoctoral contract (FJCI-2017-32593) and MD-G by a contract from Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR, (Generalitat de Catalunya, 2018FI_B1_00213). CIBEREHD, CIBERER, CIBERESP and CIBERONC are funded by the Instituto de Salud Carlos III. This research was supported by grants from Fondo de Investigación Sanitaria/FEDER (14/00613, 16/00766, 17/00509, 17/00878), Fundación Científica de la Asociación Española contra el Cáncer (GCB13131592CAST), Spanish Ministry of Science, Innovation and Universities, co-funded by FEDER funds, (SAF2016-80888-R), PERIS (SLT002/16/00398, SLT002/16/0037, Generalitat de Catalunya), CERCA Programme (Generalitat de Catalunya) and Agència de Gestió d'Ajuts Universitaris i de Recerca (Generalitat de Catalunya, GRPRE 2017SGR21, GRC 2017SGR653, 2017SGR1282, 2017SGR723). This article is based upon work from COST Action CA17118, supported by European Cooperation in Science and Technology (COST).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the corresponding institutional ethics committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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