Association Between Genetic Variation Of LMO1 Gene And The Risk Of Wilms Tumor

Wilms Tumor(WT)is one of the most common pediatric malignancies worldwide.The pathogenesis of WT is related to the genetic variation of individuals.The genome-wide association study(GWAS)suggests that the LIM domain only 1(LMO1)may increase the risk of WT.Moreover,an association has been found between LMO1 gene polymorphisms and the susceptibility to WT.Objective:To investigate the association between the four single nucleotide polymorphisms(SNPs)of LMO1 gene(rs110419 A>G,rs4758051 G>A,rs10840002 A>G and rs204938 A>G)found by GWAS and the risk of WT and to explore the relationship between five potential functional SNPs of LMO1 gene(rs2168101 G> T,rs1042359 A> G,rs11041838 G> C,rs2071458 C> A and rs3750952 G> C)and their susceptibilities to WT.Methods:This is a case-control study involving 145 children with WT and 531 normal children.TaqMan method was used to genotype the four SNPs(rs110419 A>G,rs4758051 G>A,rs10840002 A>G and rs204938 A>G)of LMO1 gene and five potential functional SNPs of the LMO1 gene(rs2168101 G> T,rs1042359 A> G,rs11041838 G> C,rs2071458 C> A and rs3750952 G> C).Statistical methods such as univariate and multivariate Logistic regression analysis were used to calculate the odds ratio(OR)and 95% confidence interval(CI)of the risk of each genotype,and analyze the association between each genotype and the genetic susceptibility to WT.Result:1.Among the four polymorphisms,only rs1140419 A>G was associated with WT risk,which was lower for children with the AG genotype than for those with the AA genotype(adjusted OR = 0.62,95% CI = 0.41-0.94,P = 0.024).2.Among the five polymorphisms,we observed that the rs2168101 G>T polymorphism corresponded to a significant decrease in WT susceptibility(GT vs.GG: adjusted OR=0.58,95% CI=0.39-0.38,P=0.010;and GT/TT vs.GG: adjusted OR=0.67,95% CI =0.46-0.97,P=0.034).3.The stratification analysis indicated that the rs110419 AG/GG genotype was more likely to reduce WT risk in males(crude OR = 0.60,95% CI = 0.36-0.996,P = 0.048),but this association disappeared after adjustment for age and gender(adjusted OR = 0.61,95% CI = 0.36-1.01,P = 0.057).4.The risk for developing WT was significantly greater in individuals carrying one to four risk genotypes than in those with no risk genotypes(adjusted OR = 1.84,95% CI = 1.25-2.69,P = 0.002).5 The predisposition to WT was significantly greater in children with one to four risk genotypes than in those with no risk genotypes.This relationship was significant in children who were over 18 months old,female,and in clinical stages III+IV(adjusted OR = 2.69,95% CI = 1.57-4.61,P = 0.0003),female(adjusted OR = 2.67,95% CI = 1.47-4.85,P = 0.001),and in clinical stages III+IV(adjusted OR = 2.16,95% CI = 1.31-3.55,P = 0.002).6.Carriers of 3-5 protective genotypes had significantly lower disease risk than carriers of 0-2 protective genotypes(adjusted OR=0.62,95% CI=0.42-0.91,P=0.022).7.The stratified analysis showed that the protective effect of rs2168101 GT/TT was predominant in males WT children,and rs2071458 GT/TT was predominant in females WT children.Regarding the combined risk genotypes,the analysis indicated that the 3-5 protective genotypes collectively decreased WT risk in females patients.Conclusion:1.This is the first report of an association between a LMO1 gene polymorphism and WT susceptibility in Chinese children.2.The rs1140419 A>G polymorphism in LMO1 may reduce the susceptibility to WT in a Southern Chinese population.3.The LMO1 gene rs2168101 G> T polymorphism may help prevent WT.4.Having 3-5 protective genotypes together reduces the risk of WT in women.