Dataset Information

The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.

ABSTRACT: Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB-E2F1 pathway. A polymorphism in the 3' UTR of E2F1 gene may disrupt a binding site for miRNA and may affect its transcription level, thus modifying the susceptibility to radiotherapy and outcomes through this pathway. We evaluated the association of a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) with risk of recurrence of SCCOP in a cohort of 1008 patients. Log-rank test and univariate and multivariable Cox models were used to evaluate the associations. Compared with patients with E2F1-rs3213180 GG homozygous genotype, the patients with E2F1-rs3213180GC+CC variant genotypes had significantly better disease-free survival (log-rank P<.001) and decreased risk of SCCOP recurrence (HR, 0.4, 95% CI, 0.3-0.5) after multivariable adjustment. Furthermore, among patients with HPV16-positive tumors, the patients with E2F1-rs3213180 GC+CC variant genotypes had significantly better disease-free survival rates (log-rank P<.001) and lower recurrence risk than those with E2F1-rs3213180 GG homozygous genotype (HR, 0.2, 95% CI, 0.1-0.4). Our findings suggest that E2F1-rs3213180 polymorphism may modulate the risk of recurrence in SCCOP patients, particularly for patients with HPV16-positive tumors of SCCOP. However, future larger population and functional studies are warranted to validate these results.

SUBMITTER: Zhang H

PROVIDER: S-EPMC6078938 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.

Zhang Hua H Sturgis Erich E Zhu Lijun L Lu Zhongming Z Tao Ye Y Zheng Hongliang H Li Guojun G

Translational oncology 20180322 3

Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB-E2F1 pathway. A polymorphism in the 3' UTR of E2F1 gene may disrupt a binding site for miRNA and may affect its transcription level, thus modifying the susceptibility to radiotherapy and outcomes through this pathway. We evaluated the association of a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) with risk of recurrence of SCCOP in a cohort of 1008 patients. Log-rank test and univariate and multi ...[more]

PMID: 29574328

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Project description:We investigated the clinical characteristics, prognostic factors, and post-recurrence prognostic factors of early- and late-recurrence patients for nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiation therapy (IMRT). This was a single-center retrospective analysis of patients in China from January 2010 to December 2015. The prognostic factors for overall survival (OS) and post-recurrence OS of early- and late-recurrence patients were identified using univariate and multivariate Cox regression analyses. Of the 9,468 patients included, 409 (4.3%), 325 (3.4%), and 182(1.9%) developed purely local recurrence, purely regional recurrence, and locoregional recurrence during follow-up, respectively. In the purely local recurrence group, 192 patients (46.9%) developed early local recurrence (ETR), and 217 patients (53.1%) developed late local recurrence (LTR). Of the 192 ETR patients, multivariate Cox regression analysis revealed that age and gender were independent risk factors of OS, and post-recurrence best supportive treatment (PRBST) was associated with poorer post-recurrence OS. Of the 217 LTR patients, the results revealed that baseline value of EBV-DNA was an independent risk factor for OS, while PRBST was associated with poorer post-recurrence OS. In the purely regional recurrence group, 183 patients (56.3%) developed early regional recurrence (ENR), and 142 patients (43.7%) developed late regional recurrence (LNR). Of the 183 ENR patients, multivariate Cox regression analysis revealed that alcohol abuse and TNM stage were independent risk factors of OS, while alcohol drinkers and PRBST were associated with poorer post-recurrence OS. Of the 142 LNR patients, PRBST was associated with poorer post-recurrence OS. In the locoregional recurrence group, 87 patients (47.8%) developed early locoregional recurrence (ELR), and 95 patients (52.2%) developed late locoregional recurrence (LLR). Of the 87 ELR patients, multivariate Cox regression analysis revealed that N stage and TNM stage were independent risk factors of OS, and N2/3 stage and PRBST were associated with poorer post-recurrence OS. Of the 95 LLR patients, the results revealed that T stage was an independent risk factor for OS, while T3/4 stage and PRBST were associated with poorer post-recurrence OS. Patients with LTR/LNR/LLR demonstrate significantly better OS compared with patients with ETR/ENR/ELR, Nevertheless, post-recurrence OS between patients with ETR/ENR/ELR and LTR/LNR/LLR was not significantly different.

Dataset Information

The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.

Publications

The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.

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