The role of genetic factors in HBV-related HCC: perspectives from local genetic backgrounds and clinical epidemiology

Familial clustering of hepatitis B surface antigen carriers (HBsAg) and hepatocellular carcinoma (HCC) has led to the evaluation of the role of genetics in hepatitis B-related diseases. Consistent reports indicate that the HLA-DP and -DQ loci are associated with persistent hepatitis B virus (HBV) infection. However, for hepatocarcinogenesis, existing studies have low power and conflicting data. Global single nucleotide polymorphism (SNP) data was collected from the 1000 Genomes Project and correlated with local epidemiological information. Southeastern Asia has a higher prevalence of HBsAg than Northeastern Asia; this was used in the evaluation of persistent HBV infection. The higher incidence of HCC in West Africa compared with East Africa was used in the evaluation of hepatocarcinogenesis. The allele frequencies for SNPs were significantly different between East Asians and Africans. Therefore, SNPs that have been identified in persistent HBV infections in East Asia may not be completely applicable in Africa. SNPs in NTCP, CTF19, and the HLA-DQ and -DP loci showed North-to-South allele frequency changes in East Asia. These findings confirm the role of genetics in persistent HBV infection. Some of the SNPs in the HLA loci show a trend of West-to-East allele frequency changes in Africa, indicating they may participate in hepatocarcinogenesis. Among the non-HLA related SNPs, rs2596542 in MICA shows a strong trend of allele frequency changes and is correlated with HCC incidence in Africa. SNPs in KIF1, IL-1A, and STAT4 also show, albeit with low statistical power, allele frequency trends compatible with HCC incidence. Taken together, there are strong correlations between background genetics in HLA-DP and -DQ loci with persistent HBV infection and hepatocarcinogenesis. The correlations were weak-positive in non-HLA loci