A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants

A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants

Abstract 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,...

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Autores principales: Mariann Unhjem Wiik, Tiffany-Jane Evans, Sami Belhadj, Katherine A. Bolton, Dagmara Dymerska, Shantie Jagmohan-Changur, Gabriel Capellá, Grzegorz Kurzawski, Juul T. Wijnen, Laura Valle, Hans F. A. Vasen, Jan Lubinski, Rodney J. Scott, Bente A. Talseth-Palmer
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/57328817e3ef4af195d6762ecb741f15
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spelling oai:doaj.org-article:57328817e3ef4af195d6762ecb741f152021-12-02T17:51:21ZA genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants10.1038/s41598-021-90501-22045-2322https://doaj.org/article/57328817e3ef4af195d6762ecb741f152021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90501-2https://doaj.org/toc/2045-2322Abstract 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.Mariann Unhjem WiikTiffany-Jane EvansSami BelhadjKatherine A. BoltonDagmara DymerskaShantie Jagmohan-ChangurGabriel CapelláGrzegorz KurzawskiJuul T. WijnenLaura ValleHans F. A. VasenJan LubinskiRodney J. ScottBente A. Talseth-PalmerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mariann Unhjem Wiik
Tiffany-Jane Evans
Sami Belhadj
Katherine A. Bolton
Dagmara Dymerska
Shantie Jagmohan-Changur
Gabriel Capellá
Grzegorz Kurzawski
Juul T. Wijnen
Laura Valle
Hans F. A. Vasen
Jan Lubinski
Rodney J. Scott
Bente A. Talseth-Palmer
A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
description Abstract 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.
format article
author Mariann Unhjem Wiik
Tiffany-Jane Evans
Sami Belhadj
Katherine A. Bolton
Dagmara Dymerska
Shantie Jagmohan-Changur
Gabriel Capellá
Grzegorz Kurzawski
Juul T. Wijnen
Laura Valle
Hans F. A. Vasen
Jan Lubinski
Rodney J. Scott
Bente A. Talseth-Palmer
author_facet Mariann Unhjem Wiik
Tiffany-Jane Evans
Sami Belhadj
Katherine A. Bolton
Dagmara Dymerska
Shantie Jagmohan-Changur
Gabriel Capellá
Grzegorz Kurzawski
Juul T. Wijnen
Laura Valle
Hans F. A. Vasen
Jan Lubinski
Rodney J. Scott
Bente A. Talseth-Palmer
author_sort Mariann Unhjem Wiik
title A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
title_short A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
title_full A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
title_fullStr A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
title_full_unstemmed A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
title_sort genetic variant in telomerase reverse transcriptase (tert) modifies cancer risk in lynch syndrome patients harbouring pathogenic msh2 variants
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/57328817e3ef4af195d6762ecb741f15
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