Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population

Wang, Dianhong; Hu, Enxi; Wu, Pei Ei; Yuan, Wenjing; Xu, Shuai; Sun, Zhe; Shi, Huaizhang; Yuan, J.; Li, Guozhong

doi:10.1007/s11060-015-1819-9

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…Somatic mutations in the promoter of TERT are found in a large proportion of adult gliomas [ 26 , 27 ], where they lead to aberrant binding of the GABP transcription factor and telomerase reactivation [ 28 ]. Our single-locus analyses show an association between inherited variation in the telomerase component genes TERC and TERT and glioma risk, as previously reported [ 1 - 3 , 29 ].…”

Section: Discussionsupporting

confidence: 89%

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

et al. 2015

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Telomere maintenance has emerged as an important molecular feature with impacts on adult glioma susceptibility and prognosis. Whether longer or shorter leukocyte telomere length (LTL) is associated with glioma risk remains elusive and is often confounded by the effects of age and patient treatment. We sought to determine if genotypically-estimated LTL is associated with glioma risk and if inherited single nucleotide polymorphisms (SNPs) that are associated with LTL are glioma risk factors. Using a Mendelian randomization approach, we assessed differences in genotypically-estimated relative LTL in two independent glioma case-control datasets from the UCSF Adult Glioma Study (652 patients and 3735 controls) and The Cancer Genome Atlas (478 non-overlapping patients and 2559 controls). LTL estimates were based on a weighted linear combination of subject genotype at eight SNPs, previously associated with LTL in the ENGAGE Consortium Telomere Project. Mean estimated LTL was 31bp (5.7%) longer in glioma patients than controls in discovery analyses (P = 7.82×10-8) and 27bp (5.0%) longer in glioma patients than controls in replication analyses (1.48×10-3). Glioma risk increased monotonically with each increasing septile of LTL (O.R.=1.12; P = 3.83×10-12). Four LTL-associated SNPs were significantly associated with glioma risk in pooled analyses, including those in the telomerase component genes TERC (O.R.=1.14; 95% C.I.=1.03-1.28) and TERT (O.R.=1.39; 95% C.I.=1.27-1.52), and those in the CST complex genes OBFC1 (O.R.=1.18; 95% C.I.=1.05-1.33) and CTC1 (O.R.=1.14; 95% C.I.=1.02-1.28). Future work is needed to characterize the role of the CST complex in gliomagenesis and further elucidate the complex balance between ageing, telomere length, and molecular carcinogenesis.

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Section: Discussionsupporting

confidence: 89%

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

et al. 2015

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“…They reported significant associations at 5p15.33 [rs2736100, P = 3.69 × 10 −4 , OR = 1.26 (1.11–1.43), 11q23.3 (rs498872, P = 3.80 × 10 −6 , OR = 1.38 (1.20–1.57) and 20q13.3 (rs6010620, P = 2.79 × 10 −6 , OR = 1.39 (1.20–1.59)], but not at 8q24.21 or 9p21.3. An additional study of 980 cases and 990 controls reported an association between rs1920116 at 3q26.2 and glioma in the Chinese population (123). Aside from these studies there is a paucity of data currently available for glioma genetic risk in non-European populations.…”

Section: Perspectives From Glioma Gwasmentioning

confidence: 99%

Genome-Wide Association Studies in Glioma

Kinnersley

Houlston

Bondy

2018

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Since the first reports in 2009, genome-wide association studies (GWAS) have been successful in identifying germline variants associated with glioma susceptibility. In this review, we describe a chronological history of glioma GWAS, culminating in the most recent study comprising 12,496 cases and 18,190 controls. We additionally summarize associations at the 27 glioma-risk SNPs that have been reported so far. Future efforts are likely to be principally focused on assessing association of germline-risk SNPs with particular molecular subgroups of glioma, as well as investigating the functional basis of the risk loci in tumor formation. These ongoing studies will be important to maximize the impact of research into glioma susceptibility, both in terms of insight into tumor etiology as well as opportunities for clinical translation.

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“…However, environmental and occupational exposures have been identi ed to be associated with the occurrence and development of glioma, especially high-dosage ionizing radiation [3]. In addition, genetic factors are also given a pivotal contribution to the occurrence and prognosis of glioma [4][5][6]. Several association studies have revealed that single nucleotide polymorphisms (SNPs) were associated with glioma risk and survival [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

Feng

Ouyang

et al. 2020

Preprint

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Background: lncRNA MIR17HG was upregulated in glioma, and participated in promoting proliferation, migration and invasion of glioma. However, the role of MIR17HG polymorphisms in the occurrence and prognosis of glioma is still unclear.Methods: In the study, 592 glioma patients and 502 control subjects were recruited. Agena MassARRAY platform was used to detect the genotype of MIR17HG polymorphisms. Logistic regression analysis was used to evaluate the relationship between MIR17HG single nucleotide polymorphisms (SNPs) and glioma risk by odds ratio (OR) and 95% confidence intervals (CIs). Kaplan–Meier curves, Cox hazards models were performed for assessing the role of these SNPs in glioma prognosis by hazard ratios (HR) and 95% CIs.Results: We found that rs7318578 (OR = 2.25, p = 3.18´10-5) was significantly associated with glioma susceptibility in the overall participants. In the subgroup with age < 40 years, rs17735387 (OR = 1.53, p = 9.05´10-3) and rs7336610 (OR = 1.35, p = 0.016) were related to the higher glioma susceptibility. More importantly, rs17735387 (HR = 0.82, log-rank p = 0.026) were associated with the longer survival of glioma patients. The GA genotype of rs17735387 had a better overall survival (HR = 0.75, log-rank p = 0.013) and progression free survival (HR = 0.73, log-rank p = 0.032) in patients with Ⅰ-Ⅱ glioma. We also found that rs72640334 was related to the poor prognosis (HR = 1.49, Log-rank p = 0.035) in female patients. In the subgroup of patients with age ³ 40 years, rs17735387 was associated with a better prognosis (HR = 0.036, Log-rank p = 0.002).Conclusion: Our study firstly reported that MIR17HG rs7318578 was a risk factor for glioma susceptibility and rs17735387 was associated with the longer survival of glioma among Chinese Han population, which might help to enhance the understanding of MIR17HG gene in gliomagenesis.

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Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population

Cited by 7 publications

References 31 publications

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk

Genome-Wide Association Studies in Glioma

Genetic variants in MIR17HG affect the susceptibility and prognosis of glioma in a Chinese Han population

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