Roles of IL-4 genetic polymorphisms and haplotypes in the risk of gastric cancer and their interaction with environmental factors.

Gastric cancer (GC) is the fifth most common cancer and imposes a global cancer burden. IL-4 is a typical cytokine of Th2 cells. IL-4 genetic polymorphisms have multiple functions in many cancers. We performed a case-control study in the Chinese population, and evaluated the association between rs2243250 (590 C/T), rs2227284 (107 T/C), rs2070874 (166 T/C) and rs1801275 (576 Q/R) and gastric cancer risk. A total of 340 gastric cancer patients and 364 controls were enrolled into our study. SNP genotyping of IL-4 rs2243250, rs2227284, rs2070874 and rs1801275 was done in a 384-well plate format on the sequenom MassARRAY platform (Sequenom, San Diego, USA). We observed the CC genotype of IL-4 rs2243250 was associated with risk of gastric cancer when compared with the TT genotype (OR=2.36, 95% CI=1.49-3.75). Moreover, individuals harboring the CT+CC genotype exposed a higher risk of gastric cancer in comparison with the TT genotype (OR=1.66, 95% CI=1.17-2.35). However, there was no significant association between IL-4 rs2227284, rs2070874 and rs1801275 and gastric cancer risk. The TT+CT genotype of IL-4 rs2243250 showed a significant increased risk of gastric cancer in males (OR=2.48, 95% CI=1.67-3.68) and those without a family history of cancer (OR=1.97, 95% CI=1.44-2.70). In ever drinkers (OR=2.04, 95% CI=1.24-3.37) and H. pylori infected patients (OR=2.31, 95% CI=1.38-3.86), the TT+CT genotype of IL-4 rs2243250 had a higher risk of gastric cancer than non-drinkers (OR=1.77, 95% CI=1.20-2.61) and non-H. pylori infected ones (OR=1.76, 95% CI=1.19-2.62). The CTCA (OR=1.54, 95% CI=1.06-2.24), CTCG (OR=1.83, 95% CI=1.16-2.86) and CTTG (OR=1.89, 95% CI=1.16-3.07) haplotypes showed an increased risk in gastric cancer, while the TCTG (OR=0.22, 95% CI=0.09-0.52), TTCG (OR=0.47, 95% CI=0.32-0.69) and TTTA (OR=0.58, 95% CI=0.42-30.79) haplotypes were associated with an reduction risk of gastric cancer. In conclusion, our study indicated that the IL-4 rs2243250 CC genotype and CT+CC genotype were associated with gastric cancer risk in the Chinese population, and IL-4 haplotypes plays an important role in the development of gastric cancer.