Author:
Wiik Mariann Unhjem,Evans Tiffany-Jane,Belhadj Sami,Bolton Katherine A.,Dymerska Dagmara,Jagmohan-Changur Shantie,Capellá Gabriel,Kurzawski Grzegorz,Wijnen Juul T.,Valle Laura,Vasen Hans F. A.,Lubinski Jan,Scott Rodney J.,Talseth-Palmer Bente A.
Abstract
AbstractIndividuals 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.
Funder
Central Norway Regional Health Authority
Cancer Institute NSW, Australia
Norwegian University of Science and Technology
University of Newcastle Australia
Publisher
Springer Science and Business Media LLC
Cited by
6 articles.
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