Association between HLA-DQ Gene Polymorphisms and HBV-Related Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Host gene variants may influence hepatitis B virus- (HBV-) related HCC. Human leukocyte antigens (HLA) play an important role in presenting virus antigens to immune cells that are responsible for the clearance of virus-infected cells and tumor cells. Previous studies have investigated the HLA-DQ (rs2856718 and rs9275572) polymorphisms that may be associated with the development of HBV-related HCC. However, the results are controversial or inconclusive. Hence, we conducted a meta-analysis to derive a more precise estimation of the associations. A total of 6 articles were used to evaluate the effect of the two polymorphisms on the risk of HBV-related HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We found that rs2856718 and rs9275572 in HLA-DQ significantly decreased HBV-related HCC in total population, especially in Chinese, but not in Saudi Arabian. Further validation of our results in larger populations and different ethnicities are required.

Figure 1

The flow charts of literature search and study selection.

Figure 2

Forest plots for HLA-DQ rs2856718 polymorphism and the risk of HBV-related HCC. (a) Overall meta-analysis of the relationship between HLA-DQ rs2856718 polymorphism and HBV-related HCC (HCC versus control) risk in dominant model (AG + GG versus AA). (b) Overall meta-analysis of the relationship between HLA-DQ rs2856718 polymorphism and HBV-related HCC (HCC versus CHB) risk in heterozygous model (AG versus AA).

Figure 3

Forest plots for HLA-DQ rs9275572 polymorphism and the risk of HBV-related HCC. (a) Overall meta-analysis of the relationship between HLA-DQ rs9275572 polymorphism and HBV-related HCC (HCC versus control) risk in dominant model (AA + AG versus GG). (b) Overall meta-analysis of the relationship between HLA-DQ rs9275572 polymorphism and HBV-related HCC (HCC versus CHB) risk in dominant model (AA + AG versus GG).

Figure 4

Sensitivity analysis of the pooled ORs and 95% CIs for HLA-DQ rs2856718 polymorphism. (a) The sensitivity analysis results of rs2856718 with HBV-related HCC (HCC versus control) in dominant model (AG + GG versus AA). (b) The sensitivity analysis results of rs2856718 with HBV-related HCC (HCC versus CHB) in heterozygous model (AG versus AA).

Figure 5

Sensitivity analysis of the pooled ORs and 95% CIs for HLA-DQ rs9275572 polymorphism. (a) The sensitivity analysis results of rs9275572 with HBV-related HCC (HCC versus control) in dominant model (AA + AG versus GG). (b) The sensitivity analysis results of rs9275572 with HBV-related HCC (HCC versus CHB) in dominant model (AA + AG versus GG).