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

Abstract

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.