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Association of NEFL Gene Polymorphisms with Wilms' Tumor Susceptibility in Chinese Children.

ABSTRACT: Wilms' tumor is renal tumor of childhood, characterized by the appearance of embryonic renal tissue and other kidney malformations. The genetic etiology of sporadic Wilms' tumor remains largely unknown. Neurofilament light (NEFL) is a tumor suppressor. We evaluated the association between three NEFL gene polymorphisms (rs11994014 G>A, rs2979704 T>C and rs1059111 A>T) and Wilms' tumor susceptibility in a Chinese population consisting of 145 cases and 531 controls. In the single locus analysis, rs2979704 CC variant genotype was associated with a decreased risk of Wilms' tumor [CC vs. TT: adjusted odds ratio (OR)=0.48, 95% confidence interval (CI)=0.24-0.94; CC vs. TT+CT: adjusted OR=0.51, 95% CI=0.27-0.97]. We also observed that carriers of the three protective genotypes had significantly decreased risk of Wilms' tumor when compared to those with 0-2 protective genotypes (adjusted OR=0.49, 95% CI=0.25-0.95). The association between rs11994014 G>A or rs1059111 A>T polymorphisms and Wilms' tumor susceptibility did not reach statistical significance. No significant association was detected in the stratified analyses. Our findings suggested that the NEFL rs2979704 T>C polymorphism may be associated with Wilms' tumor susceptibility in the Chinese population.

SUBMITTER: Jia W

PROVIDER: S-EPMC6463584 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of <i>NEFL</i> Gene Polymorphisms with Wilms' Tumor Susceptibility in Chinese Children.

Jia Wei W Zhu Jinhong J Fu Wen W Zhu Shibo S Deng Fuming F Xia Huimin H Liu Guo-Chang GC He Jing J

Journal of oncology 20190401

Wilms' tumor is renal tumor of childhood, characterized by the appearance of embryonic renal tissue and other kidney malformations. The genetic etiology of sporadic Wilms' tumor remains largely unknown. Neurofilament light (NEFL) is a tumor suppressor. We evaluated the association between three <i>NEFL</i> gene polymorphisms (rs11994014 G>A, rs2979704 T>C and rs1059111 A>T) and Wilms' tumor susceptibility in a Chinese population consisting of 145 cases and 531 controls. In the single locus analy ...[more]

PMID: 31057612

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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

Association of NEFL Gene Polymorphisms with Wilms' Tumor Susceptibility in Chinese Children.

Publications

Association of <i>NEFL</i> Gene Polymorphisms with Wilms' Tumor Susceptibility in Chinese Children.

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