YTHDF1 rs6090311 A>G polymorphism reduces Hepatoblastoma risk: Evidence from a seven-center case-control study

Various factors modulate the risk of hepatoblastoma. In this study, we aimed to investigate whether single nucleotide polymorphisms (SNPs) in the YTHDF1 gene could predispose to hepatoblastoma. We used TaqMan assay to genotype two YTHDF1 SNPs (rs6011668 C>T and rs6090311 A>G) in a Chinese population composed of 313 subjects with hepatoblastoma and 1446 controls from seven hospitals. We then evaluated the associations of these two SNPs with hepatoblastoma risk using unconditional logistic regression. We found that rs6090311 G allele exhibited a significant association with decreased hepatoblastoma risk [AG vs. AA: adjusted odds ratio (OR)=0.75; 95% confidence interval (CI)=0.58-0.98, P=0.033; AG/GG vs. AA: adjusted OR=0.76, 95% CI=0.59-0.97, P=0.029]. Furthermore, the combined analysis of protective genotypes revealed that subjects carrying two protective genotypes were less likely to have hepatoblastoma than those with 0-1 protective genotypes (adjusted OR=0.75, 95% CI=0.59-0.96, P=0.022). Subjects ≥17 months of age had decreased hepatoblastoma risk, in case that they carried rs6090311 AG/GG (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012), or two protective genotypes (adjusted OR=0.63, 95% CI=0.44-0.91, P=0.012). False-positive report probability analysis validated the reliability of the significant results. Preliminary functional annotations revealed that rs6090311 G was correlated with decreased expression of its surrounding genes in the expression quantitative trait locus (eQTL) analysis. In conclusion, our results indicate that the rs6090311 A>G in the YTHDF1 gene is related to decreased hepatoblastoma risk.