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

Yujiao Deng; Linghui Zhou; Jia Yao; Yu Liu; Yi Zheng; Si Yang; Ying Wu; Na Li; Peng Xu; Lijuan Lyu; Dai Zhang; Jun Lyu; Zhijun Dai

doi:10.1016/j.omtn.2020.02.003

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

Mol Ther Nucleic Acids. 2020 Jun 5:20:86-96. doi: 10.1016/j.omtn.2020.02.003. Epub 2020 Feb 13.

Authors

Yujiao Deng¹, Linghui Zhou¹, Jia Yao², Yu Liu², Yi Zheng¹, Si Yang¹, Ying Wu¹, Na Li¹, Peng Xu³, Lijuan Lyu³, Dai Zhang³, Jun Lyu⁴, Zhijun Dai⁵

Affiliations

¹ Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
² Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
³ Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
⁴ Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangzhou Province, China. Electronic address: lyujun2019@163.com.
⁵ Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China; Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. Electronic address: dzj0911@126.com.

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 G_rs217727A_rs2839698G_rs3741219 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.

Keywords: H19; glioma; prognosis; single nucleotide polymorphisms; susceptibility.