Interleukin-12 (IL-12) is a multifunctional cytokine that induces interferon (IFN)-γ secretion and plays an important role in antitumor immunity. The IL-12B +1188A/C polymorphism was found to correlate with a decreased cytokine production and/or activity, which may lead to increased susceptibility to cancers including hepatocellular carcinoma (HCC). Previous epidemiological studies investigating the association between IL-12B +1188A/C polymorphism and HCC risk reported inconsistent results. We performed a meta-analysis to derive a precise estimation of the association.

All studies published up to July 2014 on the association between IL-12B +1188A/C polymorphism and HCC risk were identified by searching electronic databases including PubMed, Embase, Cochrane library, and Chinese Biomedical Literature database (CBM). Data were extracted by two independent authors and the odds ratios (ORs) together with corresponding 95% confidence intervals (CIs) were used to assess the association between IL-12B +1188A/C polymorphism and HCC risk.

Five studies with 1864 cases and 2077 controls were included in the meta-analysis. We observed that the IL-12B +1188A/C polymorphism was significantly correlated with increased HCC risk when all studies were pooled into the meta-analysis (CC vs. AA: OR=1.306, 95% CI 1.063–1.606, P=0.011; AC vs. AA: OR=1.193, 95% CI 1.014–1.405, P=0.034; CC+AC vs. AA: OR=1.260, 95% CI 1.098–1.445, P=0.001). In subgroup analyses by ethnicity, source of control, and study quality, significant increased HCC risk was found in Asians, hospital-based studies, and high quality studies.

The present meta-analysis suggests that the IL-12B+1188A/C polymorphism is a low-penetrant risk factor for HCC development, especially among Asians. Further large and well-designed studies are needed to confirm this association.