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

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.