The-607C/A Polymorphisms in Interleukin-18 Gene Promoter Contributes to Cancer Risk: Evidence from A Meta-Analysis of 22 Case-Control Studies

Background: Several observational studies have investigated the association between -607 C/A polymorphism of IL-18 gene and cancer risk; however, the results were inconsistent. Therefore, we performed a meta-analysis to derive a more precise estimation of the association to help us better understand the relationship between -607 C/A polymorphism of IL-18 gene promoter and risk of cancer. Methods: A literature search was carried out using PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database between January 1966 and February 2013. Fixed-effect and random-effect models were used to estimate the pooled odds ratio (OR) and the corresponding 95% confidence intervals (CIs). Results: A total of 22 case-control studies including 4100 cancer cases and 4327 controls contributed to the analysis. Significant association between -607C/A polymorphism in IL-18 gene promoter and cancer risk was observed (CA vs CC: OR = 1.221, 95% CI: 1.096, 1.360; P-heterogeneity=0.219; AA/CA vs. CC: OR = 1.203, 95% CI: 1.057, 1.369; P-heterogeneity=0.064). In the subgroup analysis by ethnicity, -607C/A polymorphism significantly increased risk of cancer among Asian population (AA/CA vs. CC: OR = 1.197, 95% CI: 1.023,1.401; P-heterogeneity=0.088); however, no significant association was found in Caucasian or African population. The -607C/A polymorphism was associated with a significantly increased risk of nasopharyngeal carcinoma (CA vs CC: OR = 1.330, 95% CI: 1.029,1.719; P-heterogeneity=0.704; AA/CA vs. CC: OR = 1.323, 95% CI: 1.037,1.687; P-heterogeneity=0.823) and esophageal cancer (AA/CA vs. CC: OR = 1.289, 95% CI: 1.002,1.658; P-heterogeneity=0.700). Conclusions: The present meta-analysis suggests that the -607C/A polymorphisms in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially for nasopharyngeal carcinoma and esophageal cancer and in Asian population. More studies with larger sample size, well controlled confounding factors are warranted to validate this association.