Unhjem Wiik, MariannEvans, Tiffany JaneBelhadj, SamiBolton, Katherine A.Dymerska, DagmaraJagmohan Changur, ShantieCapellá, G. (Gabriel)Kurzawski, GrzegorzWijnen, Juul T.Valle, LauraVasen, HansLubinski, JanScott, Rodney J.Talseth-Palmer, Bente A.2021-07-052021-07-052021-05-31https://hdl.handle.net/2445/178839Individuals with Lynch syndrome (LS), have an increased risk of developing cancer. Common genetic variants of telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). The risk of cancer was estimated by heterozygous/homozygous odds ratio (OR) with mixed-effects logistic regression to adjust for gene/gender/country of sample origin considering family identity. The AA genotype of SNP rs2075786 is associated with 85% higher odds at developing cancer compared to GG genotype in MSH2 pathogenic variant carriers (p = 0.0160). Kaplan-Meier analysis also shows an association for rs2075786; the AA allele for MSH2 variant carriers confers risk for earlier diagnosis of LS cancer (log-rank p = 0.0011). We report a polymorphism in TERT to be a possible modifier of disease risk in MSH2 pathogenic variant carriers. The rs2075786 SNP in TERT is associated with a differential risk of developing cancer for MSH2 pathogenic variant carriers. Use of this information has the potential to personalise screening protocols for LS patients.9 p.application/pdfengcc by (c) Unhjem Wiik, Mariann et al., 2021http://creativecommons.org/licenses/by/3.0/es/CancerMalalties hereditàriesFactors de risc en les malaltiesCàncerGenetic diseasesRisk factors in diseasesinfo:eu-repo/semantics/article7133982021-07-02info:eu-repo/semantics/openAccess34059744