To the Editor: Wilms tumor, or nephroblastoma, is the most frequently diagnosed pediatric kidney cancer, accounting for >90% of all renal tumors in children 1-7 years old, and the disease may be related to genetic factors. [1] As an emerging research spot, the epitranscriptome has been implicated in different RNA modifications in human diseases, including cancers. [2] Methyltransferaselike 1 (METTL1), a critical RNA N7-methylguanosine (m7G) methyltransferase, can catalyze the formation of a m7G modification (mostly at nucleotide position 46 in the variable region of transfer RNAs [tRNAs]) by complexing with WD repeat domain 4 (WDR4). Depending on the different positions, the tRNA m7G modifications have various functions. In particular, the tRNA modifications located in the anticodon region play a crucial role in translation and growth, while those outside the anticodon region are responsible for the regulation of tRNA folding, stability, and protein synthesis. The m7G modification is evolutionarily conserved and has more complicated and important physiological functions in mammals. [3] Increasing evidence strongly supports that the dysregulation or mutation of METTL1 m7G methyltransferase is closely associated with tumorigenesis and poor prognosis. [2] Mechanistically, an underlying molecular mechanism has been identified for how METTL1-mediated m7G modification leads to malignant transformation and tumorigenesis. Orellana et al [2] discovered that an m7G modification of tRNAs is
Wilms tumor is the most common embryonal renal malignancy in children. WDR4 is an indispensable noncatalytic subunit of the RNA N7-methylguanosine (m7G) methyltransferase complex and plays an essential role in tumorigenesis. However, the relationship between polymorphisms in the WDR4 gene and susceptibility to Wilms tumor remains to be fully investigated. We performed a large case-control study involving 414 patients and 1199 cancer-free controls to investigate whether single nucleotide polymorphisms (SNPs) in the WDR4 gene are associated with Wilms tumor susceptibility. WDR4 gene polymorphisms (rs2156315 C > T, rs2156316 C > G, rs6586250 C > T, rs15736 G > A, and rs2248490 C > G) were genotyped using the TaqMan assay. In addition, unconditioned logistic regression analysis was performed, odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between WDR4 gene SNPs and Wilms tumor susceptibility as well as the strength of the associations. We found that only the rs6586250 C>T polymorphism was significantly associated with an increased risk of Wilms tumor (adjusted OR=2.99, 95% CI = 1.28-6.97, P = 0.011 for the rs6586250 TT genotype; adjusted OR=3.08, 95% CI = 1.33-7.17, P = 0.009 for the rs6586250 CC/CT genotype). Furthermore, the stratification analysis revealed that patients with the rs6586250 TT genotype and carriers with 1-5 risk genotypes exhibited statistically significant associations with increased Wilms tumor risk in specific subgroups. However, the rs2156315 CT/TT genotype was identified as having a protective effect against Wilms tumor in the age >18 months subgroup compared with the rs2156315 CC genotype. In brief, our study demonstrated that the rs6586250 C > T polymorphism of the WDR4 gene was significantly associated with Wilms tumor. This finding may contribute to the understanding of the genetic mechanism of Wilms tumor.
Aim: To survey the association between LIN28B gene polymorphisms and the increased risk of Wilms' tumor (WT). Methods: Five LIN28B polymorphisms (rs314276 C>A, rs221634 A>T, rs221635 T>C, the rs4145418 A>C and rs9404590 T>G) were genotyped in 355 WT patients and 1070 healthy controls to assess the association. Result: The rs314276 CA/AA genotype was a protective factor against WT (corrected odds ratio [OR]: 0.71; p = 0.006). Individuals older than 18 months (corrected OR: 0.60; p = 0.001), males (corrected OR: 0.65; p = 0.011) and in clinical stage I + II patients (corrected OR: 0.60; p = 0.0008) with this genotype were less susceptible to WT. Conclusion: The rs314276 CA/AA genotype may protect against WT.
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