PT - JOURNAL ARTICLE AU - Arnau-Collell, Coral AU - Soares de Lima, Yasmin AU - Díaz-Gay, Marcos AU - Muñoz, Jenifer AU - Carballal, Sabela AU - Bonjoch, Laia AU - Moreira, Leticia AU - Lozano, Juan José AU - Ocaña, Teresa AU - Cuatrecasas, Miriam AU - Díaz de Bustamante, Aranzazu AU - Castells, Antoni AU - Capellà, Gabriel AU - Bujanda, Luis AU - Cubiella, Joaquin AU - Rodríguez-Alcalde, Daniel AU - Balaguer, Francesc AU - Ruiz-Ponte, Clara AU - Valle, Laura AU - Moreno, Victor AU - Castellvi-Bel, Sergi TI - Colorectal cancer genetic variants are also associated with serrated polyposis syndrome susceptibility AID - 10.1136/jmedgenet-2019-106374 DP - 2020 Oct 01 TA - Journal of Medical Genetics PG - 677--682 VI - 57 IP - 10 4099 - http://jmg.bmj.com/content/57/10/677.short 4100 - http://jmg.bmj.com/content/57/10/677.full SO - J Med Genet2020 Oct 01; 57 AB - 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.