Abstract: Objective To investigate the association of genetic variants in eukaryotic translation initiation factor 3 (eIF3) and the risk of hepatitis B virus⁃related hepatocellular carcinoma(HBV⁃HCC). Methods A two⁃stage case⁃control study was performed in this study. The single nucleotide polymorphisms (SNP) loci associated with HCC risk were selected in the discovery stage included 966 HCC cases and 1003 hepatitis B surface antigen (HBsAg) positive controls from Guangxi. In the validation stage, the  480 HCC cases and 484 HBsAg positive controls from Shanghai were used to validate the positive loci in the discovery stage. The association between genetic variants of eIF3 and the risk of HBV⁃HCC was analyzed by univariable and multivariable logistic regression. Results The results showed that two potential functional SNPs (rs7401 A>G and rs23057952 A>G) in 3'⁃UTR of EIF3G were associated with the risk of HBV⁃HCC. Compared with the A allele carriers, rs7401 G allele carriers had an increased risk of HBV⁃HCC (OR=1.18, 95%CI: 1.02-1.38, P=0.028). While, rs2305795 G allele reduced the risk of HBV⁃HCC compared with the A allele (OR=0.74, 95%CI: 0.64-0.86, P<0.001). Combined analysis showed a dose⁃response manner between the number of unfavorable genotypes (rs7401 AG/GG genotypes and rs2305795 AA genotype) and the increased risk of HBV⁃HCC (Ptrend<0.001). Expression quantitative trait loci (eQTL) analysis revealed that both rs7401 G allele and rs2305795 A allele were significantly associated with increased EIF3G mRNA expression level, which were significantly higher in HCC tissues than in normal tissues. Conclusions EIF3G rs7401 G allele and EIF3G rs2305795 A allele can increase the risk of HBV⁃HCC.

Key words:  Hepatocelluar carcinoma, Hepatitis B virus, eIF3, Single nucleotide polymorphisms, Risk