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Associations of lncRNA H19 Polymorphisms at MicroRNA Binding Sites with Glioma Susceptibility and Prognosis.

ABSTRACT: Glioma is the most common tumor of the central nervous system; variation in susceptibility and prognosis worldwide suggests that there are molecular and genetic differences among individuals. The H19 gene plays a dual role in carcinogenesis. In this study, associations between H19 polymorphisms and susceptibility as well as prognosis in glioma were evaluated. In total, 605 patients with glioma and 1,300 cancer-free subjects were enrolled in the study. Individuals with the rs3741219 A>G allele were less likely to develop glioma (relative risk [RR] = 0.54, 95% confidence interval [95% CI] = 0.45-0.63, p < 0.001), whereas rs217727 G>A and rs2839698 G>A genotypes were not associated with glioma risk. The associations between H19 polymorphisms and prognosis were assessed, including overall survival and progression-free survival. Three focused H19 polymorphisms did not show a significant effect on survival. Further analysis based on false-positive report probability validated these significant results. In the haplotype analysis, individuals with the Grs217727Ars2839698Grs3741219 haplotype were less likely to develop glioma (odds ratio [OR] = 0.33, 95% CI = 0.23-0.46, p = 0.02). Overall, carriers of the rs3741219 AG or GG genotype of H19 have a decreased susceptibility to glioma, but polymorphisms in this gene are not related to prognosis.

SUBMITTER: Deng Y

PROVIDER: S-EPMC7062941 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Associations of lncRNA H19 Polymorphisms at MicroRNA Binding Sites with Glioma Susceptibility and Prognosis.

Deng Yujiao Y Zhou Linghui L Yao Jia J Liu Yu Y Zheng Yi Y Yang Si S Wu Ying Y Li Na N Xu Peng P Lyu Lijuan L Zhang Dai D Lyu Jun J Dai Zhijun Z

Molecular therapy. Nucleic acids 20200213

Glioma is the most common tumor of the central nervous system; variation in susceptibility and prognosis worldwide suggests that there are molecular and genetic differences among individuals. The H19 gene plays a dual role in carcinogenesis. In this study, associations between H19 polymorphisms and susceptibility as well as prognosis in glioma were evaluated. In total, 605 patients with glioma and 1,300 cancer-free subjects were enrolled in the study. Individuals with the rs3741219 A>G allele we ...[more]

PMID: 32155588

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Project description:BACKGROUND:Dysfunction of the circadian clock and polymorphisms of some circadian genes have been linked to cancer development and progression. We investigated the relationship between circadian genes germline variation and susceptibility or prognosis of patients with soft tissue sarcoma. PATIENTS AND METHODS:We considered the 14 single nucleotide polymorphisms (SNPs) of 6 core circadian genes that have a minor allele frequency >?5% and that are known to be associated with cancer risk or prognosis. Genotyping was performed by q-PCR. Peripheral blood and clinic-pathological data were available for 162 patients with liposarcoma or leiomyosarcoma and 610 healthy donors. Associations between the selected clock genes polymorphisms and sarcoma susceptibility or prognosis were tested assuming 3 models of inheritance: additive, recessive and dominant. Subgroup analysis based on sarcoma histotype was performed under the additive genetic model. Multivariate logistic regression and multivariate Cox proportional hazard regression analyses were utilized to assess the association between SNPs with patient susceptibility and survival, respectively. Pathway variation analysis was conducted employing the Adaptive Rank Truncated Product method. RESULTS:Six out of the 14 analyzed SNPs were statistically significantly associated with susceptibility or prognosis of soft tissue sarcoma (P <?0.05). The present analysis suggested that carriers of the minor allele of the CLOCK polymorphism rs1801260 (C) or of PER2 rs934945 (T) had a reduced predisposition to sarcoma (26% and 35% respectively with the additive model) and liposarcoma (33% and 41% respectively). The minor allele (A) of NPAS2 rs895520 was associated with an increased predisposition to sarcoma of 33% and leiomyosarcoma of 44%. RORA rs339972 C allele was associated with a decreased predisposition to develop sarcoma assuming an additive model (29%) and leiomyosarcoma (36%). PER1 rs3027178 was associated with a reduced predisposition only in liposarcoma subgroup (32%). rs7602358 located upstream PER2 was significantly associated with liposarcoma survival (HR: 1.98; 95% CI 1.02-3.85; P?=?0.04). Germline genetic variation in the circadian pathway was associated with the risk of developing soft tissue sarcoma (P?=?0.035). CONCLUSIONS:Genetic variation of circadian genes appears to play a role in the determinism of patient susceptibility and prognosis. These findings prompt further studies to fully dissect the molecular mechanisms.

Dataset Information

Associations of lncRNA H19 Polymorphisms at MicroRNA Binding Sites with Glioma Susceptibility and Prognosis.

Publications

Associations of lncRNA H19 Polymorphisms at MicroRNA Binding Sites with Glioma Susceptibility and Prognosis.

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