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

Abstract

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.

SNPs in the interleukin-12 signaling pathway are associated with breast cancer risk in Puerto Rican women

“…Previously, IL-12-related genetic associations studies have centered their focus specifically in the heterodimeric IL-12 molecule (encoded by the IL12A and IL12B genes). Several meta-analyses have summarized the associations of these IL-12 genes and cancer risk [ 23 , 24 , 38 ]. For the IL12A gene, the SNPs rs568048 has been one of the most published [ 20 , 38 ].…”

“…Several meta-analyses have summarized the associations of these IL-12 genes and cancer risk [ 23 , 24 , 38 ]. For the IL12A gene, the SNPs rs568048 has been one of the most published [ 20 , 38 ]. This SNP was not found to be associated with BC risk in our study population.…”

A new discovery of STAT4 single nucleotide polymorphisms associated with hepatocellular carcinoma risk in Chinese Han population: a case–control study

“…Therefore, the research on the association between STAT4 genetic polymorphism and the susceptibility of HCC has attracted more and more attention. Many studies have reported that STAT4 gene polymorphisms have a certain association with the susceptibility of HCC, especially the association between STAT4 rs7574865 and the susceptibility of HCC has been reported many times (12)(13)(14)(15). However, the results of their research are not exactly the same, so the molecular mechanism of HCC susceptibility has not yet been clarified.…”

Associations between hepatocellular carcinoma risk and rs3212227 and rs568408 polymorphisms: a systematic review and meta-analysis

“…However, Tan et al 9 reported conflicting findings, and found no significant association between this polymorphism and an increased risk for HCC. Xiao et al 27 identified the STAT4 rs7574865 polymorphism as a risk factor for HCC, but failed to find any significant association between HCC risk and other polymorphisms in genes related to the IL-12 signaling pathway, including IL12A rs568408 and IL12B rs3212227. In contrast, the current meta-analysis indicated that rs568408 polymorphisms in the IL-12 gene were significantly correlated with HCC risk, suggesting that the AA wild-type IL-12 genotype may protect against HCC tumorigenesis, especially among individuals of Chinese ethnicity.…”