Role of FTO gene polymorphisms in Wilms tumor predisposition: A five‐center case–control study

Abstract

Background: Wilms tumor is the most frequently occurring renal malignancy in pediatrics. The FTO gene exhibits a featured genetic contribution to cancer development.Nonetheless, its single nucleotide polymorphism (SNP) contribution to Wilms tumor remains unknown.Methods: In the present study, 402 Wilms tumor patients and 1198 healthy controls were successfully genotyped for FTO gene SNPs (rs1477196 G>A, rs9939609 T>A, rs7206790 C>G and rs8047395 A>G) using TaqMan SNP genotyping assays. Odds ratios (ORs) and 95% confidence intervals (CIs), generated from unconditional logistic regression, were applied to quantify the effects of FTO gene SNPs on Wilms tumor risk.Results: We found that the rs8047395 A>G polymorphism was significantly correlated with an increased risk for Wilms tumor (GG versus AA/AG: adjusted OR = 1.38, 95% CI = 1.04-1.85, p = 0.027). Carriers with 1 and 1-2 risk genotypes are more susceptible of developing Wilms tumor than those without risk genotypes. Stratified analysis of rs8047395 and risk genotypes revealed more significant relationships with Wilms tumor risk in certain subgroups. Preliminary functional annotations revealed that the rs8047395 A allele increases expression levels of the FTO gene as determined by expression quantitative trait locus analysis. Conclusions:The present study provides evidence that rs8047395 may regulate FTO gene expression and thus confer susceptibility to Wilms tumor. The candidate FTO gene rs8047395 A>G polymorphism identified in this study warrants independent investigation.

The controversial role and therapeutic development of the m6A demethylase FTO in renal cell carcinoma

“…Consistent with these findings, Hua et al. reported that in 402 Wilms tumor patients and 1198 healthy controls, the rs8047395 A allele polymorphism in FTO was significantly correlated with elevated FTO expression and increased risk for Wilms tumor, the most common pediatric renal malignancy [27] . Although the expression level of FTO in ccRCC tissues remains divisive, these results suggest FTO might play an important oncogenic role in kidney cancer in both children and adults.…”

ALKBH1 rs2267755 C>T polymorphism decreases neuroblastoma risk in Chinese children

“…Its balance is synergistically regulated by methyltransferases (METTL4) and demethylase (ALKBH1, ALKBH4). Methylation-related studies demonstrated that genetic variants of the methylation-related genes could affect tumor susceptibility 12 , 29 , 30 . Our group previously genotyped 5 N6-methyladenosine (m6A) methylase METTL14 SNPs in 898 neuroblastoma patients and 1734 control samples.…”

“…Consistent with FTO and ALKBH5, ALKBH1 is a member of the AlkB family, which catalyzes substrate demethylation in Fe (II)- and α-ketoglutarate-dependent manner 32 . Previous research found that the FTO ( ALKBH9 ) gene SNP rs8047395 A>G variant is significantly correlated with Wilms tumor 29 . And the ALKBH5 gene SNPs had a weak impact on hepatoblastoma risk 33 .…”

Genetic Variants of SIRT1 Gene Promoter in Type 2 Diabetes

“…SIRT1 gene expression was not measured directly with clinical samples due to lack of sample availability. Moreover, the effects of the SNPs (g.4540A > G (rs3740051) and g.4821G > T (rs35995735)) on SIRT1 gene expression need further study, as have been by previous studies [ 62 , 63 ]. In addition, the impact of the SNPs on the onset and progression of T2D needs to be investigated.…”