Association of the YTHDF2 rs3738067 A>G variant with hepatoblastoma risk: a multicenter case-control study in Chinese children

As a rare cancer, hepatoblastoma is the most prevalent malignant liver tumor in children, yet its underlying causes are poorly understood. YTHDF2, a canonical m⁶A reader, regulates mRNA stability and decay, and its dysregulation has been implicated in tumorigenesis across multiple malignancies. Whether YTHDF2 polymorphisms influence hepatoblastoma risk is unclear. This multicenter case-control study was therefore designed to analyze the YTHDF2 rs3738067 A > G variant in Chinese children. We recruited 313 hepatoblastoma cases and 1446 controls from seven hospitals across China for this case-control study. The YTHDF2 rs3738067 A > G polymorphism was genotyped using the TaqMan PCR method. We assessed its association with hepatoblastoma risk using multivariate logistic regression to calculate adjusted odds ratios and 95% confidence intervals, controlling for age and sex. Comprehensive analyses of this multi-center Chinese pediatric cohort revealed that the YTHDF2 rs3738067 A > G polymorphism was not associated with hepatoblastoma risk in any analysis, including the overall population and all stratified subgroups. These findings suggest that this specific YTHDF2 variant may not be a key risk factor for hepatoblastoma in Chinese children. Future studies incorporating diverse ethnic populations and investigating other polymorphisms, alone or in combination, are warranted to confirm these findings and explore potential associations.