Abstract
BackgroundWilms tumor is a frequently diagnosed renal cancer among children with unclear genetic causes. N6‐methyladenosine (m6A) modification genes play critical roles in tumorigenesis. However, whether genetic variations of m6A modification genes predispose to Wilms tumor remain unclear. ALKBH5 (AlkB homolog 5), a crucial member of m6A modification genes, encodes a demethylase that functions to reverse m6A RNA methylation.MethodsHerein, we evaluated the association of single nucleotide polymorphisms (SNPs) in the m6A modification gene ALKBH5 and Wilms tumor susceptibility in a large multi‐center case‐control study. A total of 414 Wilms tumor cases and 1199 healthy controls were genotyped for ALKBH5 rs1378602 and rs8400 polymorphisms by TaqMan.ResultsNo significant association was detected between these two polymorphisms and Wilms tumor risk. Moreover, 1, 2, and 1‐2 protective genotypes (rs1378602 AG/AA or rs8400 GG) did not significantly reduce Wilms tumor risk, compared with risk genotypes only. Stratification analysis revealed a significant relationship between rs1378602 AG/AA genotypes and decreased Wilms tumor risk in children in clinical stage I diseases [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.32‐0.98, P = .042]. The presence of 1‐2 protective genotypes was correlated with decreased Wilms tumor risk in subgroups of age > 18 months, when compared to the absence of protective genotypes (adjusted OR = 0.74, 95% CI = 0.56‐0.98, P = .035).ConclusionCollectively, our results demonstrate that ALKBH5 SNPs may exert a weak influence on susceptibility to Wilms tumor. This finding increases the understanding of the role of the m6A gene in tumorigenesis of Wilms tumor.
Highlights
Wilms tumor is a common embryonal kidney that mostly affects children.[1]
This work was motivated by the discovery of m6A modification genes as critical cancer regulators and the emerging role of m6A gene SNPs in cancer susceptibility
We attempted to investigate whether ALKBH5 gene SNPs could link to the risk of Wilms tumor
Summary
Wilms tumor is a common embryonal kidney that mostly affects children.[1]. It is typically characterized by the disorganized and dysregulated development of a kidney.[2,3] The prevalence of Wilms tumor is about 7-10 per million in Western countries, while it is only 3.3 per million in China.[2,4] Nearly 95% of cases are diagnosed under ten years old, with mean diagnosis age at 43-48 months.[5]. The genetic variants in the m6A genes are referred to as the m6A-associated SNPs (m6A-SNPs).[29] The m6A modification has become a research hotspot yet studies on the association between m6A-SNPs and cancer risk are very scarce. It is urgent to explore the effect of m6A-SNPs on cancer risk, which can provide a new perspective of the etiology of cancer and of the role of m6A. We conducted the first case-control study of 414 Wilms tumor cases and 1199 controls to yield new insights into the role of m6A modification gene ALKBH5 SNPs in Wilms tumorigenesis
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