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A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants
- Source :
- 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
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- 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
- Accession number :
- edsair.doi.dedup.....87a7a4b98fab8066172bacbc5e011305