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.
Highlights
Wilms tumor is the most common pediatric renal malignancy [1]
Our results indicated that the rs12587 GT genotype is a risk variant for Wilms tumor (Table 1), as individuals with this genotype had a 1.30-fold greater risk for developing Wilms tumor (95% confidence interval [CI]=1.004-1.68, P=0.046) than those with the GG genotype
We further examined the combined effects of the risk genotypes for KRAS on Wilms tumor risk
Summary
Wilms tumor (nephroblastoma) is the most common pediatric renal malignancy [1]. It is normally derived from embryonal kidney precursor cells in which cell growth and/or differentiation are dysregulated during development [2, 3]. Clark et al demonstrated that coordinated activation of RAS and βcatenin accelerated the growth and metastatic progression of Wilms tumor in a murine model [28] They later reported that activating KRAS mutations were found in human Wilms tumor samples [29]. Another team verified the importance of RAS mutations in the development and progression of Wilms tumor [30]. Despite these findings, the link between RAS gene polymorphisms and Wilms tumor risk remains obscure. To clarify the association of RAS with Wilms tumor risk, we selected single-nucleotide polymorphisms (SNPs) in the two most common diseased-related RAS genes, KRAS and NRAS, for analysis in a four-center hospital-based case-control study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
