A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
| Autor: | Dagmara Dymerska, Grzegorz Kurzawski, Gabriel Capellá, Katherine A. Bolton, Hans F. A. Vasen, Juul T. Wijnen, Rodney J. Scott, Shantie Jagmohan-Changur, Tiffany-Jane Evans, Bente A. Talseth-Palmer, Jan Lubinski, Mariann Unhjem Wiik, Sami Belhadj, Laura Valle |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine 0302 clinical medicine Genotype Malalties hereditàries Càncer Cancer genetics Telomerase Cancer Aged 80 and over Genetics Multidisciplinary Factors de risc en les malalties RNA-Directed DNA Polymerase Middle Aged Lynch syndrome MutS Homolog 2 Protein 030220 oncology & carcinogenesis Chromosomes Human Pair 5 Medicine Female Colorectal Neoplasms Genetic diseases Adult Adolescent Risk factors in diseases Science MLH1 Polymorphism Single Nucleotide Article Young Adult 03 medical and health sciences medicine Humans Genetic Predisposition to Disease Allele Aged business.industry Odds ratio medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis digestive system diseases MSH6 030104 developmental biology MSH2 business |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Dipòsit Digital de la UB Universidad de Barcelona Scientific Reports Scientific Reports, 11(1). NATURE RESEARCH |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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