METTL14 gene polymorphisms decrease Wilms tumor susceptibility in Chinese children.

Background: Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (mA) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility.

Methods: A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay.

Result: Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0-4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes.

Conclusions: Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.