Page 132 - Read Online

Page 10 of 12 Tai et al. Hepatoma Res 2020;6:74 I http://dx.doi.org/10.20517/2394-5079.2020.54

incidence of HCC in East Africa than in West Africa [Table 6]. It should be noted that the function of
miRNA-122 is complicated and that the frequency of this insertion variant in East Asians (0.704) is much
higher than in Africans (0.199; Table 4). If this SNP is associated with HCC, then it will have a significant
impact in East Asians.

Rs187238 is located upstream of interleukin-18 (IL-18) (-148 G>C). The G allele induces increased IL-18
[54]
mRNA expression compared to the C allele . The frequency of the G allele is lower in HCC cases than
in non-HCC cases. This implies that those with a stronger immunity may be able to control HBV and
hepatocarcinogenesis. However, a follow-up study did not validate the allele differences between HCC and
[55]
non-HCC5 cases . In this review, the G-allele frequency was higher in West than in East Africa (0.248 to
0.152; Table 6), contradicting the higher incidence of HCC in West Africa. The incident epidemiology does
not support rs187238 playing a role in hepatocarcinogenesis in Africans. This does not necessarily provide
evidence against the association of this SNP with hepatocarcinogenesis in East Asians. Termination of HBV
replication is more important in East Asians than in Africans.

[56]
Rs1048338 in PRSS23 has been identified by GWAS to be associated with HCC in China . However,
no other report has validated this observation. A trend of a higher C allele frequency in West compared
to East Africa (0.412 to 0.273, P = 0.001384; Table 6) has also been observed. This finding is not against
the association rs1048338 with hepatocarcinogenesis. However, more studies are needed to confirm its
association with HBV-related HCC.

CONCLUSION
We confirm that there are significant differences in genetic background between Africa and East Asia. By
correlating genetic backgrounds with clinical epidemiology, we have found that the allele frequency of
HLA-DQ and -DP loci do explain a higher prevalence of HBsAg in Southeastern compared to Northeastern
Asia. Some of these SNPs also showed West-to-East changes in allele frequency in Africa and are correlated
with HCC incidence. For the non-HLA loci, SNPs in NTCP and CTF19 showed allele frequency trends
from North-to-South in East Asians, supporting their association with fighting in persistent HBV infection.
There is a strong correlation between allele frequency and HCC incidence on SNPs located in MICA
and weak positive correlations in KIF1, STAT4, and IL1A. The studies concerning genetic factors and
hepatocarcinogenesis are difficult since multiple factors are involved and different genetic backgrounds
exist among the study populations.

DECLARATIONS
Acknowledgments
We would like to thank Uni-edit (www.uni-edit.net) for editing and proofreading this manuscript.

Authors’ contributions
Designed the study and wrote the manuscript: Tai DI
Collected and organized data: Tai J

Availability of data and materials
The data source is from the 1000 Genomes Project (http://www.1000genomes.org/).

Financial support and sponsorship
This research was supported by the grant from Chang Gung Memorial Hospital (CMRPG3F0331).

Conflicts of interest
Both authors declared that there are no conflicts of interest.