Association between polymorphisms in interleukin‐17A and interleukin‐17F genes and risks of gastric cancer

Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori‐induced gastric cancer. Interleukin (IL)‐17A and IL‐17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case–control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL‐17A G197A and IL‐17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) and DNA sequencing. Logistic regression and Cox‐proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL‐17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22–1.87 for GA; OR 1.61, 95% CI: 1.03–2.51 for GG]. Further stratification analyses indicated that the effect of IL‐17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL‐17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40–65‐year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL‐17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL‐17A 197 may be less relevant.