Dataset Information

Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk: a four-center case-control study.

ABSTRACT: Wilms tumor is a type of pediatric solid tumor that arises partly due to somatic and germline mutations. Single-nucleotide polymorphisms (SNPs) in the RAS gene reportedly modify the risk for several types of human malignancies. We conducted a multicenter study to investigate whether RAS gene variants predispose individuals to Wilms tumor. Four SNPs in RAS were genotyped in 355 Wilms tumor cases and 1070 controls. The SNPs included rs12587 G>T, rs7973450 A>G and rs7312175 G>A in KRAS, and rs2273267 A>T in NRAS. Individuals harboring the rs12587 GT genotype were more likely to develop Wilms tumor than those carrying the GG genotype (adjusted odds ratio [OR]=1.30, 95% confidence interval [CI]=1.004-1.68, P=0.046). However, the other three SNPs seemed not to influence the risk for Wilms tumor. Compared to individuals without a risk genotype, those harboring one to three KRAS risk genotypes had an adjusted OR of 1.28 for developing Wilms tumor (95% CI=1.002-1.64, P=0.048). Stratification analysis revealed that rs12587 GT/TT was associated with Wilms tumor risk in children >18 months old (adjusted OR=1.39, 95% CI=1.02-1.89, P=0.037). Our findings indicate that the rs12587 G>T polymorphism in KRAS is associated with increased Wilms tumor susceptibility.

SUBMITTER: Fu W

PROVIDER: S-EPMC6428095 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk: a four-center case-control study.

Fu Wen W Zhuo Zhenjian Z Hua Rui-Xi RX Fu Kai K Jia Wei W Zhu Jinhong J Zhang Jiao J Cheng Jiwen J Zhou Haixia H Xia Huimin H He Jing J Liu Guochang G

Aging 20190301 5

Wilms tumor is a type of pediatric solid tumor that arises partly due to somatic and germline mutations. Single-nucleotide polymorphisms (SNPs) in the RAS gene reportedly modify the risk for several types of human malignancies. We conducted a multicenter study to investigate whether RAS gene variants predispose individuals to Wilms tumor. Four SNPs in RAS were genotyped in 355 Wilms tumor cases and 1070 controls. The SNPs included rs12587 G>T, rs7973450 A>G and rs7312175 G>A ...[more]

PMID: 30860980

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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 KRAS and NRAS gene polymorphisms with Wilms tumor risk: a four-center case-control study.

Publications

Association of <i>KRAS</i> and <i>NRAS</i> gene polymorphisms with Wilms tumor risk: a four-center case-control study.

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