H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study

Abstract

Background Wilms tumor is the most common pediatric renal cancer. However, genetic bases behind Wilms tumor remain largely unknown. H19 is a critical maternally imprinted gene. Previous studies indicated that nucleotide polymorphisms (SNPs) in the H19 can modify the risk of several human malignancies. Epigenetic errors at the H19 locus lead to biallele silencing in Wilms tumors. Genetic variations in the H19 may be related to Wilms tumor susceptibility. Methods We conducted a four-center study to investigate whether H19 SNPs was a predisposing factor to Wilms tumor. Three polymorphisms in the H19 (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) were genotyped in 355 cases and 1070 cancer-free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. Results We found that all of these three polymorphisms were significantly associated with Wilms tumor risk alterations. Carriers of 1, 2 and 1-2 risk genotypes were inclined to develop Wilms tumor compared with those without risk genotype (adjusted OR=1.36, 95% CI=1.02-1.80, P=0.037; adjusted OR=1.84, 95% CI=1.27-2.67, P=0.001; adjusted OR=1.50, 95% CI=1.17-1.92, P=0.002, respectively). The stratified analysis further revealed that rs2839698 AA, rs217727 AA, and 1-2 risk genotypes could strongly increase Wilms tumor risk among male patients above 18 months of age.Conclusion Our findings indicate that genetic variations in the H19 may confer Wilms tumor risk.

LncRNA OSTM1-AS1 acts as an oncogenic factor in Wilms’ tumor by regulating the miR-514a-3p/MELK axis

“…For example, the lncRNA MEG3 has been reported to be underexpressed in WT and inhibit the growth and metastasis of WT cells in vitro by regulating the Wnt/β-catenin pathway [8]. The polymorphism of lncRNA H19 is significantly associated with the risk of WT [9]. Moreover, the expression of lncRNA myocardial infarction associated transcript (MIAT) in WT is remarkably increased, and deletion of MIAT inhibits the growth and metastasis of tumor cells [10].…”