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 G rs217727 A rs2839698 G 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.

Genetic Interaction of H19 and TGFBR1 Polymorphisms with Risk of Epilepsy in a Chinese Population

“…Notably, a significant three-loci interaction model of rs3741219-rs2839698-rs6478974 was identified to increase the risk of epilepsy. Our results were consistent with some previous reports in central nervous system diseases, which found that the G rs217727 A rs2839698 G rs3741219 haplotype carriers were less likely to develop glioma 39 and the 3-loci model of rs2280543-rs217727-rs2839698 conferred the risk of intracranial aneurysm. 40 With regard to the association between H19 polymorphisms and risk ischemic stroke (IS), conflicting results were obtained.…”

The Good, the Bad, the Question–H19 in Hepatocellular Carcinoma

“…Interestingly, this region encodes for the antisense transcript HOTS. But so far, there is no evidence for a co-expression of H19 and HOTS in vivo [86]. In HCC, the T allele of H19 rs217727 polymorphism, which is associated with decreased H19 expression, enhanced the survival rate of patients with HCC [101].…”

“…Nevertheless, it is essential to compare these results with human HCC samples. Most human studies show that H19 is overexpressed in HCC [28,30,66,[86][87][88][89][90][91]. Early investigations indicated an elevation of H19 in human HCC samples [32,[89][90][91].…”

“…In fact, in colorectal cancer, IGF2 expression is unrelated to its imprinting status [100], which might be also the case also for H19. n = 359 n = 1190 controls -gene polymorphisms and specific haplotype of H19 increased susceptibility to hepatocellular carcinoma [87] n = 944 -rs2839698 SNP of lncRNA-H19 was associated with an increased risk of HCC [102] n = 214 -polymorphism of rs217727 in H19 was associated with HCC [101] Two other exciting studies investigate the association between different H19 polymorphisms and the susceptibility as well as prognosis on tumorigenesis [86,87]. A study in glioma by Deng et al with 605 patient samples showed that some polymorphisms decreased susceptibility to glioma, a common and highly fatal brain tumor [86].…”

Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan

“…The “T” allele at H19 rs2839698 was reported to be associated with bladder cancer [ 25 ], renal cell carcinoma [ 34 ], ovarian cancer [ 35 ], hepatoblastoma [ 36 ], hepatoma cell carcinoma [ 37 , 38 ], gastric cancer [ 39 ], colorectal cancer [ 40 , 41 ], and breast cancer [ 42 ]. Meanwhile, H19 rs2839698 was reported not to be associated with oral cancer [ 43 ], lung cancer [ 44 ], cervical cancer [ 45 ], glioma [ 46 ], and neuroblastoma [ 47 , 48 ]. On the contrary, H19 rs217717 was reported to be associated with altered risks of hepatoblastoma [ 36 ], gastric cancer [ 39 ], oral cancer [ 43 ], and lung cancer [ 44 ], while whether the “T” allele is a risk or protective is still controversial [ 26 , 42 , 49 ].…”