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

Date Published: March 15, 2019

Publisher: Impact Journals

Author(s): Wen Fu, Zhenjian Zhuo, Rui-Xi Hua, Kai Fu, Wei Jia, Jinhong Zhu, Jiao Zhang, Jiwen Cheng, Haixia Zhou, Huimin Xia, Jing He, Guochang Liu.


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.

Partial Text

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]. The incidence rate of Wilms tumor is about 1 in 10,000 children in Western countries [4]. The overall five-year survival rate exceeds 90% in developed countries [5–7]. Despite great achievements in the treatment of Wilms tumor, the outcomes for patients with high-risk disease (about 25%) remain disappointing [8]. Apart from this, high treatment costs and severe chronic health conditions that occur in nearly 25% of survivors are also challenging [9,10].

Thus far, only a small portion of genetic loci have been found to increase the risk of Wilms tumor. This underscores the need to reveal more genetic loci that could predispose individuals to this disease. Herein, we evaluated the impact of KRAS and NRAS gene SNPs on the risk of Wilms tumor in 355 Wilms tumor patients and 1070 healthy control subjects. To the best of our knowledge, we are the first to report the association of RAS gene polymorphisms with Wilms tumor risk in Chinese children.




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