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Neuro-Oncology
Article
Data sources: UnpayWall
Neuro-Oncology
Article . 2013 . Peer-reviewed
Data sources: Crossref
Neuro-Oncology
Article . 2014
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Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis

Authors: Walsh, Kyle M; Rice, Terri; Decker, Paul A; Kosel, Matthew L; Kollmeyer, Thomas; Hansen, Helen M; Zheng, Shichun; +18 Authors

Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis

Abstract

Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. We examined associations of these 7 established glioma risk loci with age at diagnosis among patients with glioma.SNP genotype data were available for 2286 Caucasian glioma patients from the University of California, San Francisco (n = 1434) and the Mayo Clinic (n = 852). Regression analyses were performed to test for associations between "number of risk alleles" and "age at diagnosis," adjusted for sex and study site and stratified by tumor grade/histology where appropriate.Four SNPs were significantly associated with age at diagnosis. Carrying a greater number of risk alleles at rs55705857 (CCDC26) and at rs498872 (PHLDB1) was associated with younger age at diagnosis (P = 1.4 × 10(-22) and P = 9.5 × 10(-7), respectively). These SNPs are stronger risk factors for oligodendroglial tumors, which tend to occur in younger patients, and their association with age at diagnosis varied across tumor subtypes. In contrast, carrying more risk alleles at rs2736100 (TERT) and at rs6010620 (RTEL1) was associated with older age at diagnosis (P = 6.2 × 10(-4) and P = 2.5 × 10(-4), respectively). These SNPs are risk factors for all glioma grades/histologies, and their association with age at diagnosis was consistent across tumor subgroups.Carrying a greater number of risk alleles might be expected to decrease age at diagnosis. However, glioma susceptibility conferred by variation in telomerase-related genes did not follow this pattern. This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres).

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Keywords

Prevention (rcdc), Male, Aging, Neoplasm Grading (mesh), Aging (rcdc), Clinical Research (rcdc), Brain Disorders (rcdc), single nucleotide polymorphism, Risk Factors, glioma, Glioma (mesh), 2.1 Biological and endogenous factors, 32 Biomedical and Clinical Sciences (for-2020), Male (mesh), Telomerase, Neurosciences (rcdc), Genetic Predisposition to Disease (mesh), Cancer, Cancer (rcdc), Brain Cancer (rcdc), Humans (mesh), telomere, Tumor, Follow-Up Studies (mesh), Brain Neoplasms, Age Factors, Single Nucleotide, Glioma, 1112 Oncology and Carcinogenesis (for), Middle Aged, Prognosis, age at diagnosis, Female, DNA Helicases (mesh), Tumor (mesh), Brain Neoplasms (mesh), Adult, Single Nucleotide (mesh), Genotype, Oncology and Carcinogenesis, 610, telomerase, Polymorphism, Single Nucleotide, Case-Control Studies (mesh), 618, Rare Diseases (rcdc), Rare Diseases, Telomerase (mesh), Clinical Research, Risk Factors (mesh), Middle Aged (mesh), Genetics, Biomarkers, Tumor, 3211 Oncology and carcinogenesis (for-2020), Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Polymorphism, Aged, Biomedical and Clinical Sciences, Genetics (rcdc), Aged (mesh), Genotype (mesh), Prevention, Human Genome, Neurosciences, DNA Helicases, 2.1 Biological and endogenous factors (hrcs-rac), Prognosis (mesh), Human Genome (rcdc), 1109 Neurosciences (for), Brain Disorders, Brain Cancer, 3211 Oncology and Carcinogenesis (for-2020), Oncology & Carcinogenesis (science-metrix), Female (mesh), Case-Control Studies, Adult (mesh), Neoplasm Grading, Age Factors (mesh), Biomarkers, Follow-Up Studies

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
43
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Top 10%
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