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J Med Genet. 2020 Mar 13. pii: jmedgenet-2019-106374. doi: 10.1136/jmedgenet-2019-106374. [Epub ahead of print]

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

Author information

1
Gastroenterology 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
Bioinformatics Platform, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
3
Pathology 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
Genetics Unit, Hospital Universitario de Mostoles, Mostoles, Spain.
5
Hereditary 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
Gastroenterology 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
Gastroenterology 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
Digestive Disease Section, Hospital Universitario de Mostoles, Mostoles, Spain.
9
Fundación 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
Unit 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.
11
Gastroenterology 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 sbel@clinic.cat.

Abstract

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

PMID:
32170005
DOI:
10.1136/jmedgenet-2019-106374
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Conflict of interest statement

Competing interests: None declared.

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