Systematic Review and Meta-Analysis on the Association between Polymorphisms in Genes of IL-12 Signaling Pathway and Hepatocellular Carcinoma Risk

We performed an updated meta-analysis and systematic review to explore the associations between polymorphisms in genes of IL-12 signaling pathway and hepatocellular carcinoma (HCC) risk. Diverse databases were retrieved to identify entire available studies, and odds ratios (ORs) correspondence with 95% confidence intervals (CIs) were performed to assess their associations. Finally, 6 polymorphisms in five genes of the IL-12 signaling pathway were extracted from 39 case-control studies, 26 publications. We identified that STAT4-rs7574865 polymorphism was significantly associated with an increased risk of HCC in allelic contrast, dominant, homozygote and recessive models. However, we failed to uncover any significant association between other polymorphisms in genes of IL-12 signaling pathway and HCC risk, including IL18-rs1946518 and -rs187238, IFN-γ-rs2430561, IL12A-rs568408, IL12B-rs3212227 and STAT4-rs7574865. When the subgroup analysis was conducted based on Hardy-Weinberg Equilibrium (HWE) status, we identified that IFN-γ-rs2430561 polymorphism was significantly associated with an increased risk of HCC in homozygote and recessive models of these studies whose control groups were conformed to HWE. To sum up, our study suggests that STAT4-rs7574865 is a risk factor for HCC. Further well-designed large sample size studies are warranted to shed new light on these findings.