The -137G>C polymorphism in interleukin-18 promoter region and cancer risk: evidence from a meta-analysis of 21 studies.

Interleukin-18 (IL-18) is a key cytokine responsible for immune response and involved in the process of cancer development. The association of -137G>C polymorphism in the promoter region of IL-18 with cancer risk is still elusive based on current genetic association studies. We performed this meta-analysis to determine whether the -137G>C polymorphism is associated with cancer risk. A comprehensive search was conducted for databases of PubMed, EMBASE, and China National Knowledge Infrastructure. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association strength. Publication bias was detected by Egger's and Begg's test. Twenty-one eligible studies including 3,498 cancer patients and 5,222 controls were identified and analyzed. In the overall analysis, no significant association between -137G>C polymorphism and cancer risk was observed. In the sub-group analyses of ethnicities, the -137G>C polymorphism significantly increased cancer risk in Asian population (GC/CC vs. GG: OR = 1.313, 95% CI = 1.053-1.638, heterogeneity P < 0.001) but not in Caucasian population. Further stratified analyses showed that the variant -137C allele was significantly associated with increased risk of nasopharyngeal carcinoma (C vs. G: OR = 1.484, 95% CI = 1.193-1.847, heterogeneity P = 0.213). No publication bias was detected. We provide evidence that the -137G>C polymorphism in IL-18 promoter region significantly increases cancer risk in Asian population but not in Caucasian population, and the variant -137C allele is associated with increased risk of nasopharyngeal carcinoma.