Associations of common IL-4 gene polymorphisms with cancer risk: A meta-analysis

Cancer incidence is dramatically increasing worldwide, therefore improved prediction and therapeutic methods are needed. Single nucleotide polymorphisms in cytokine genes may contribute to carcinogenesis. Interleukin (IL)-4 gene polymorphisms have been intensively studied with regard to their associations with cancer. However, the results of these previous studies remain inconclusive. The present study, therefore, aimed to conduct a meta-analysis of previously published studies in order to clarify the association of IL-4 with cancer risk. Eligible published articles were searched in Medline, PubMed, Embase and China National Knowledge Infrastructure databases up to March 2016. Odds ratios and 95% confidence intervals were used to identify potential associations between IL-4 genetic polymorphisms and the risk of cancer. A meta-analysis was then performed on 10,873 patients and 14,328 controls for IL-4 rs2243250 polymorphism, 3,970 patients and 5,686 controls for IL-4 rs2070874 polymorphism, and 1,896 patients and 2,526 controls for IL-4 rs79071878 polymorphism. A significant association with cancer risk was observed for rs2243250 and rs79071878 polymorphisms. In the subgroup analysis by cancer type, rs2243250 polymorphism was demonstrated to be associated with an increased risk of gastric cancer and breast cancer, rs2070874 polymorphism was correlated with leukemia and oral carcinoma, and rs79071878 polymorphism was relevant to bladder carcinoma risk. In the subgroup analysis by ethnicity, IL-4 rs2243250 polymorphism was demonstrated to be associated with cancer risk in both Caucasian and Asian populations, rs2070874 was associated with cancer risk in Asian populations, while rs79071878 polymorphism was associated with cancer risk in Caucasian populations. In conclusion, the present results suggested that the IL-4 rs2243250 and rs79071878 polymorphisms were associated with cancer susceptibility. Further subgroup analyses revealed that the effects of IL-4 gene polymorphisms on cancer risk may vary by cancer type and by ethnicity.