Effect of interleukin-17A and interleukin-17F gene polymorphisms on the risk of gastric cancer in a Chinese population

• The rs2275913 AA and rs3748067 TT genotypes are associated with an increased risk of gastric cancer.
• The rs9382084 TT genotype was marginally significantly associated with an increased risk of gastric cancer.
• The rs2275913 and rs3748067 genetic variants have combined effects with H. pylori infection on gastric cancer risk.
• The rs3748067 and rs9382084 genetic variants have interaction with tobacco smoking on gastric cancer risk.
• The rs2275913, rs3748067 and rs9382084 genetic variants greatly increase risk of non-cardia gastric cancer.

We selected six tagged single-nucleotide polymorphisms (SNPs) in the IL-17A and IL-17F genes, and evaluated the relationship between the six common SNPs and H. pylori infection, tobacco smoking and subsites of gastric cancer in gastric cancer patients. Genotyping of IL-17A (rs2275913, rs3748067 and rs3819025) and IL-17A (rs763780, rs9382084, and rs12203582) was performed in a 384-well plate format on the MassARRAY® platform. An unconditional multiple logistical regression model was performed to determine the association between IL-17A and IL-17F genetic variations and gastric cancer risk. Unconditional logistic regression analysis showed that subjects carrying the rs2275913AA and rs3748067 TT genotypes were 1.70 and 3.45 times more likely to develop gastric cancer. Furthermore, rs2275913 and rs3748067 genetic variants significantly interacted with H. pylori infection on the risk of gastric cancer. The interaction between rs3748067 and rs9382084 genetic variants and tobacco smoking trend was significant. In addition, rs2275913, rs3748067 and rs9382084 genetic variants were only associated with non-cardia gastric cancer. The findings suggest that the rs2275913, rs3748067 and rs9382084 polymorphisms increase the risk of gastric cancer, and they interact with H. pylori infection, tobacco smoking and subsites of gastric cancer. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.