Association of IL-8 gene promoter −251 A/T and IL-18 gene promoter −137 G/C polymorphisms with head and neck cancer risk: a comprehensive meta-analysis

PURPOSE: No consensus exists on the impact of polymorphisms in cytokines (such as interleukin IL-8 and IL-18) on cancer risk; moreover, there is very little evidence regarding head and neck cancer (HNC). METHODS: Thus, a meta-analysis including 22 studies with 4731 cases and 8736 controls was conducted to evaluate this association. The summary odds ratio (OR) and corresponding 95% confidence intervals (CIs) for C-X-C motif chemokine ligand 8 (CXCL8, which encodes IL-8) and IL-18 polymorphisms and HNC risk were estimated. RESULTS: The results showed a significantly increased risk of HNC susceptibility for IL18 −137 G/C in five genetic models, but, interestingly, no significant association was found for the CXCL8 −251 A/T polymorphism. When stratified by cancer type, an increased risk of nasopharyngeal cancer was found for both −137 G/C and −251A/T. When the studies were stratified by ethnicity and genotyping method, there were significant associations between Asian populations and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) studies for −137 G/C, and African populations for −251 A/T in some genetic models. A positive association was also found between the population-based groups in some models for −137 G/C; conversely, significantly decreased risk was found among the −251 A/T hospital-based group. Meta-regression was also conducted. The publication year, control source, and cancer type contributed to CXCL8 −251 A/T heterogeneity; however, no factors were found that contributed to IL-18 −137 G/C heterogeneity. Marginal significance was found in the recessive model for IL-18 −137 G/C by Egger’s test, whereas no publication bias was detected for CXCL8 −251 A/T. CONCLUSIONS: The results indicate that the IL-18 −137 G/C polymorphism is associated with HNC risk, especially nasopharyngeal cancer, in Asian populations and, when using PCR-RFLP, CXCL8 −251 A/T polymorphisms play a complex role in HNC development.