Background: Previous studies have suggested that IL4, IL13, and IL4R are associated with serum IgE levels and allergies, and common variants of these genes may alter cancer risk. To clarify these associations, we conducted a meta-analysis to investigate the associations of IL4 , IL13 , and IL4R polymorphisms with gastrointestinal cancer risk.

Methods: We used 27 eligible case–control studies describing the associations of six polymorphisms of IL4 , IL13 , and IL4R with gastrointestinal cancer risk to calculate summary odds ratios (ORs) and 95% confidence intervals (CIs) using five different genetic models. The Q-statistic and I² statistic were calculated to examine heterogeneity.

Results: The IL4 rs2070874 T allele seems to be associated with an increased risk of gastrointestinal cancer (OR 1.11; 95% CI, 1.00–1.24 for T allele vs . C allele). This association was significant in studies conducted outside of Asia (OR 1.28; 95% CI, 1.03–1.58 for T allele vs . C allele) and in studies investigating the association with gastric cancer (OR 1.17; 95% CI, 1.03–1.34 for T allele vs . C allele). However, the IL4R rs1801275 heterozygote seems to be associated with a reduced risk of gastrointestinal cancer (OR 0.79; 95% CI, 0.65–0.96 for AG vs . AA). Other polymorphisms did not show any significant associations with gastrointestinal cancer risk in any of the genetic models and subgroup analyses.

Conclusions: Our results suggest that certain polymorphisms of IL4 and IL4R may affect susceptibility to gastrointestinal cancer. However, further studies are required to confirm these findings.