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oai:recercat.cat:2445/1788392025-12-05T13:18:05Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917

urn:hdl:2445/178839 A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants Unhjem Wiik, Mariann Evans, Tiffany Jane Belhadj, Sami Bolton, Katherine A. Dymerska, Dagmara Jagmohan Changur, Shantie Capellá, G. (Gabriel) Kurzawski, Grzegorz Wijnen, Juul T. Valle, Laura Vasen, Hans Lubinski, Jan Scott, Rodney J. Talseth-Palmer, Bente A. Cancer Malalties hereditàries Factors de risc en les malalties Càncer Genetic diseases Risk factors in diseases Individuals 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. 2021-07-05T11:07:07Z 2021-07-05T11:07:07Z 2021-05-31 2021-07-02T12:00:36Z info:eu-repo/semantics/article Reproducció del document publicat a: https://doi.org/10.1038/s41598-021-90501-2 Scientific Reports, 2021, vol. 11, num. 11401 https://doi.org/10.1038/s41598-021-90501-2 cc by (c) Unhjem Wiik, Mariann et al., 2021 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Springer Science and Business Media LLC Articles publicats en revistes (Ciències Clíniques)