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The association of RAN and RANBP2 gene polymerphisms with Wilms tumor risk in Chinese children.

ABSTRACT: Wilms tumor is considered to be the most common renal malignancy among children. RAN, a member of RAS superfamily, and its binding partner RANBP2 are related to the progression of multiple tumors. Nevertheless, the effects of the RAN and RANBP2 gene polymorphisms on the tumorigenesis of Wilms tumor remain unclarified. In this study, three potentially functional polymorphisms (rs56109543 C>T, rs7132224 A>G, and rs14035 C>T) in the RAN and one (rs2462788 C>T) in the RANBP2 were chosen to investigate their association with Wilms tumor susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess the association of the selected polymorphisms with Wilms tumor susceptibility. Results shown that RAN rs7132224 AG/GG genotypes significantly increased Wilms tumor risk when compared to AA genotype (adjusted OR=1.40, 95% CI=1.01-1.95, P=0.047). Carriers of 1-3 risk genotypes have a significantly higher Wilms tumor risk than those without risk genotype (adjusted OR=1.49, 95% CI=1.07-2.07, P=0.020). Moreover, stratified analysis indicated that RAN rs56109543 CT/TT genotypes, RAN rs7132224 AG/GG genotypes and RANBP2 rs2462788 CT/TT genotypes remarkably increased Wilms tumor susceptibility among the subgroups. Our results indicated that RAN and RANBP2 polymorphisms were associated with Wilms tumor susceptibility in Chinese children. The role of RAN/RANBP2 in cancers deserves more attention.

SUBMITTER: Huang X

PROVIDER: S-EPMC6959007 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The association of RAN and RANBP2 gene polymerphisms with Wilms tumor risk in Chinese children.

Huang Xiaokai X Zhao Jie J Fu Wen W Zhu Jinhong J Lou Susu S Tian Xiaoqian X Chen Shanshan S Ruan Jichen J He Jing J Zhou Haixia H

Journal of Cancer 20200101 4

Wilms tumor is considered to be the most common renal malignancy among children. RAN, a member of RAS superfamily, and its binding partner RANBP2 are related to the progression of multiple tumors. Nevertheless, the effects of the RAN and RANBP2 gene polymorphisms on the tumorigenesis of Wilms tumor remain unclarified. In this study, three potentially functional polymorphisms (rs56109543 C>T, rs7132224 A>G, and rs14035 C>T) in the RAN and one (rs2462788 C>T) in the RANBP2< ...[more]

PMID: 31949483

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Project description:BackgroundWilms 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 single nucleotide polymorphisms (SNPs) in the H19 can modify the risk of several human malignancies. Epigenetic errors at the H19 locus lead to biallelic silencing in Wilms tumors. Genetic variations in the H19 may be related to Wilms tumor susceptibility.MethodsWe conducted a four-center study to investigate whether H19 SNP 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.ResultsWe found that all of these three polymorphisms were significantly associated with Wilms tumor risk alterations. The rs2839698 G > A polymorphism (AG vs. GG: adjusted OR = 0.74, 95% CI = 0.57-0.96, p = 0.024; AA vs. GG: adjusted OR = 1.52, 95% CI = 1.05-2.22, p = 0.027), the rs3024270 C > G polymorphism (CG vs. CC: adjusted OR = 0.61, 95% CI = 0.46-0.81, p = 0.0007; and the rs217727 polymorphism (AG vs. GG: adjusted OR = 0.76, 95% CI = 0.58-0.99, p = 0.035). The 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 children above 18 months of age, males, and with clinical stage I+II disease.ConclusionOur findings indicate that genetic variations in the H19 may confer Wilms tumor risk.

Dataset Information

The association of RAN and RANBP2 gene polymerphisms with Wilms tumor risk in Chinese children.

Publications

The association of <i>RAN</i> and <i>RANBP2</i> gene polymerphisms with Wilms tumor risk in Chinese children.

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