Purpose: Increasing investigations have been performed on the association of -607C/A polymorphism in Interleukin-18 (IL-18) gene promoter with cancer risk and have yielded conflicting results. To derive a more precise estimation of the association, we performed an updated meta-analysis of all eligible studies.
Methods: We searched all eligible studies by using PubMed, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs) were pooled by the fixed-effects/random-effects model in STATA 12.0 software.
Results: This meta-analysis included 29 studies with 6,026 cases and 6,476 controls. Overall, significantly increased cancer risk was observed (A vs C: OR=1.10, 95% CI: 1.01,1.19, Pheterogeneity=0.001; AA vs CC: OR=1.17, 95% CI: 1.01,1.37, Pheterogeneity=0.007; CA vs CC: OR=1.15, 95% CI: 1.05,1.25, Pheterogeneity=0.152; AA/CA vs CC: OR=1.17, 95% CI: 1.06,1.31, Pheterogeneity=0.042). In subgroup analyses based on ethnicity, the results suggested a significantly increased risk of cancer in Asian population (CA vs CC: OR=1.11, 95% CI: 1.00-1.24, Pheterogeneity=0.353; AA/CA vs CC: OR=1.14, 95% CI: 1.02-1.29, Pheterogeneity=0.081) and in Mixed population (A vs C: OR=1.72, 95% CI: 1.22-2.43, Pheterogeneity=NA; AA vs CC: OR=2.84, 95% CI: 1.43-5.64, Pheterogeneity=NA; AA vs CC/CA: OR=2.43, 95% CI: 1.34-4.42, Pheterogeneity=NA; AA/CA vs CC: OR=1.69, 95% CI: 1.00-2.85, Pheterogeneity=NA); however, no significant association was found in Caucasian or African populations. In the subgroup analysis by cancer type we found a significantly increased susceptibility to breast cancer (A vs C: OR=1.33, 95% CI: 1.00-1.75,Pheterogeneity=0.155; AA vs CC: OR=1.80, 95% CI: 1.02-3.21,Pheterogeneity=0.162; AA7sol;CA vs CC: OR=1.33, 95% CI: 1.00-1.78,Pheterogeneity=0.546), nasopharyngeal carcinoma (A vs C: OR=1.16, 95% CI: 1.01-1.32, Pheterogeneity=0.921; AA vs CC: OR=1.34, 95% CI: 1.02-1.75, Pheterogeneity=0.863; CA vs. CC: OR=1.36, 95% CI: 1.08-1.70, Pheterogeneity=0.824; AA/CA vs CC: OR=1.35, 95% CI: 1.09-1.68,Pheterogeneity=0.904), and esophageal cancer (CA vs CC: OR=1.37, 95% CI: 1.04-1.80, Pheterogeneity=0.528; AA/CA vs CC: OR =1.29, 95% CI: 1.00-1.66, Pheterogeneity=0.700).
Conclusions: The current meta-analysis suggests that the -607C/A polymorphism in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma and esophageal cancer and in Asian and Mixed populations. More studies with diverse ethnic groups, larger sample size, and well controlled confounding factors are warranted to further investigate the association.