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Background   Several previous studies have assessed the relationship between IL-4-590C/T gene polymorphism and smoking-related cancer in recent years; however, the results remain controversial. Based on it, the study intends to clarify whether IL-4-590C/T variant increases the risk of smoking-related cancer through meta-analysis.Methods   We searched PubMed, EMBASE, Web of Science, Cochrane Library database, China National Knowledge Infrastructure, and Wanfang data information service platform to collect qualified case-control studies in strict accordance with the inclusion and exclusion standards. The 95% confidence interval (95% CI) and its odds ratio (OR) were adopted to access the relation between IL-4-590C/T gene polymorphism and smoking-related cancer; sensitivity analysis and publication bias assessment were carried out after the studies' quality evaluation.Results   17 studies were included in total, with 5,061 patients and 6,346 control cases. A significant association between IL-4-590C/T variant and smoking-related cancer in total population was revealed in our meta-analysis results, and IL-4-590C/T variant might have a relatively protective effect on smoking-related cancer (CT vs. TT:  P =0.026, OR = 0.900, 95% CI: 0.820–0.987). Subgroup analysis by ethnicity showed that the IL-4-590C/T polymorphism was associated with a decreased risk of smoking-related cancer in the Asian population (CT vs. TT:  P =0.008, OR = 0.878, 95% CI: 0.798–0.967; CC + CT vs. TT:  P =0.030, OR = 0.903, 95% CI: 0.824–0.990). Subgroup analysis based on types of cancer demonstrated the IL-4-590C/T variant achieved a lower risk in renal cell cancer (CC vs. TT:  P =0.046, OR = 0.640, 95% CI: 0.412–0.993).Conclusion   There is a conspicuous association between IL-4-590C/T polymorphism and decreased risk of smoking-related cancer, particularly in Asians. And IL-4-590C/T polymorphism may have a protective effect on renal cell cancer.

Effects of IL-4-590C/T (rs2243250) Polymorphism on the Susceptibility of Smoking-Related Cancer: A Meta-Analysis Involving 11,407 Subjects