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LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four-centre case-control study.

ABSTRACT: Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. Overall, we found that rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumour. Combination analysis of risk genotypes showed that, compared to non-carriers, subjects with 1 risk genotype and 1-3 risk genotypes were more likely to develop Wilms tumour, with an adjusted odds ratio (OR) of 1.58 and 1.56, respectively. Stratified analysis further demonstrated that the risk effect remained prominent in some subgroups. We also found that presence of 1-3 risk genotypes was associated with Wilms tumour risk in subgroups > 18 months of age, females, males and those with clinical stage I + II diseases. Furthermore, expression quantitative trait locus (eQTL) analysis indicated that rs3811463 C allele was significantly associated with increased transcripts of LIN28A gene. These findings suggest that LIN28A gene polymorphisms may be associated with increased predisposition to Wilms tumour.

SUBMITTER: Zhuo Z

PROVIDER: S-EPMC6787499 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four-centre case-control study.

Zhuo Zhenjian Z Fu Wen W Liu Jiabin J Cheng Jiwen J Zhou Haixia H Zhang Jiao J Zhu Jin-Hong JH Xia Huimin H Liu Guochang G He Jing J

Journal of cellular and molecular medicine 20190723 10

Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. O ...[more]

PMID: 31338973

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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.

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LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four-centre case-control study.

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LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four-centre case-control study.

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