期刊
JOURNAL OF MEDICAL GENETICS
卷 57, 期 10, 页码 677-682出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jmedgenet-2019-106374
关键词
serrated polyposis syndrome; colorectal cancer; genetic association study; low-penetrance genetic variant; genetic predisposition to disease
资金
- 'la Caixa' Foundation [LCF/BQ/DI18/11660058, 100010434, 713673]
- Juan de la Cierva postdoctoral contract [FJCI-2017-32593]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca, AGAUR, (Generalitat de Catalunya) [2018FI_B1_00213]
- Instituto de Salud Carlos III
- Fondo de Investigacion Sanitaria/FEDER [14/00613, 16/00766, 17/00509, 17/00878]
- Fundacion Cientifica de la Asociacion Espanola contra el Cancer [GCB13131592CAST]
- FEDER funds [SAF201680888--R]
- PERIS (Generalitat de Catalunya) [SLT002/16/00398, SLT002/16/0037]
- CERCA Programme (Generalitat de Catalunya)
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (Generalitat de Catalunya) [GRPRE 2017SGR21, GRC 2017SGR653, 2017SGR1282, 2017SGR723]
- European Cooperation in Science and Technology (COST) [CA17118]
- Spanish Ministry of Science, Innovation and Universities
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). TheGREM1risk 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-EIF3Hand rs3217810-CCND2.
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