Associations of IL-4, IL-4R, IL-17A, and IL-17F Polymorphisms with Colorectal Cancer Risk: A Meta-Analysis, Meta-Regression, and Trial Sequential Analysis

Both interleukin (IL)-4 and IL-17 polymorphisms may be involved in the pathogenesis and progression of colorectal cancer (CRC). Herein, we designed a meta-analysis to assess the associations between IL-4, IL-4R, IL-17A, and IL-17F polymorphisms and CRC risk. Scopus, Web of Science, Cochrane Library, and PubMed databases were searched to retrieve articles published until October 21, 2021. We used crude odds ratio (OR) and 95% confidence interval assessing the association of the polymorphisms and CRC risk in 5 genetic models. Trial sequential analysis for the primary analyses was used to control random errors. Twenty-three studies (8: IL-4 rs2243250, 4: IL-4R rs1801275, 5: IL-17A rs2275913, and 6: IL-17F rs763780) were involved in the meta-analysis. The pooled OR (P-value) for the association between IL-4 rs2243250 polymorphism and the CRC risk was 1.11 (0.08), 1.27 (0.12), 1.07 (0.37), 1.09 (0.17), and 1.22 (0.12), for IL-4R rs1801275 polymorphism was 0.71 (0.18), 1.05 (0.76), 0.86 (0.37), 0.87 (0.41), and 0.69 (0.39), for IL-17A rs2275913 polymorphism was 1.83 (0.0003), 1.73 (0.06), 1.47 (<0.001), 1.61 (0.001), and 1.42 (0.15), and for IL-17F rs763780 polymorphism was 1.07 (0.48), 5.33 (0.02), 1.08 (0.49), 1.08 (0.47), and 8.42 (0.002) in allelic, homozygous, heterozygous, recessive, and dominant models, respectively. The G allele and GA genotype of IL-17A rs2275913 polymorphism and the CC genotype of IL-17F rs763780 polymorphism had an elevated risk in CRC cases. The ethnicity and genotyping method, sample size, control, and publication year were effective factors on the pooled results.