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Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association between the polymorphisms of; IL-8 (-251T/A); and; IL-6 (-174G/C); and the risk of oral cancer (OC).; PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until December 18, 2020 without any restrictions. RevMan 5.3 software was used to calculate the results of forest plots (odds ratios (ORs) and 95% confidence intervals (CIs)); CMA 2.0 software was used to calculate funnel plots (Begg's and Egger's tests), and SPSS 22.0 was used for the meta-regression analysis. Moreover, trial sequential analysis was conducted to estimate the robustness of the results.; Eleven articles including twelve studies were selected for the meta-analysis. The pooled ORs for the association between; IL-8 (-251T/A); polymorphism and the risk of OC in the models of A vs. T, AA vs. TT, TA vs. TT, AA + TA vs. TT, and AA vs. TT + TA were 0.97 (; p; = 0.78), 0.86 (; p; = 0.55), 0.78 (; p; = 0.37), 0.83 (; p; = 0.45), and 1.10 (; p; = 0.34), respectively. The pooled ORs; IL-6 (-174G/C); polymorphism and the risk of OC in the models of C vs. G, CC vs. GG, GC vs. GG, CC + GC vs. GG, and CC vs. GG + GC were 1.07 (; p; = 0.87), 1.17 (; p; = 0.82), 1.44 (; p; = 0.38), 1.28 (; p; = 0.61), and 0.96 (; p; = 0.93), respectively. There was no association between; IL-8 (-251T/A); polymorphism and OC susceptibility, but the C allele and GC and CC genotypes of; IL-6 (-174G/C); polymorphism were associated with the risk of OC based on subgroup analyses, that is to say, the source of control and the genotyping method might bias the pattern of association.; The meta-analysis confirmed that there was no association between the polymorphisms of; IL-6 (-174G/C); and; IL-8 (-251T/A); and the susceptibility of OC. However, the source of control and the genotyping method could unfavorably impact on the association between the polymorphisms of; IL-6 (-174G/C); and the risk OC.
