Contribution of interaction between genetic variants of interleukin-11 and Helicobacter pylori infection to the susceptibility of gastric cancer

Abstract

Background: Gastric cancer (GC) ranks the second leading cause of cancer-related mortality worldwide. We aimed to clarify the relevance of genetic variants of IL-11, a hub of various carcinogenic pathways, as well as their interactions with Helicobacter pylori (H. pylori) infection in the development of GC.

Methods: A case-control study with 880 GC cases and 900 healthy controls was conducted in a Chinese population. Six tagSNPs were detected by Taqman Allelic Discrimination assay, while H. pylori status was detected by Typing Detection Kit for Antibody to H. pylori and serum IL-11 level was measured using ELISA method.

Results: We found that rs1126760 (C vs T: OR=1.39, 95% CIs=1.13-1.70, P=0.002) and rs1126757 (C vs T: OR=0.82, 95% CIs=0.72-0.93, P=0.002) were significantly associated with susceptibility of GC. Even adjusted for Bonferroni correction, the results were still significant (P=0.002×6=0.012). IL-11 rs1126760 was significantly associated with higher serum and expression level of IL-11, while rs1126757 was significantly associated with lower serum IL-11 level (P<0.001). Significant interaction with H. pylori infection was identified for rs1126760 (P for interaction =0.005). Higher expression of the IL-11 gene was significant with development and poor prognosis of GC.

Conclusion: Our study provides strong evidence that genetic variants of the IL-11 gene may interact with H. pylori infection and contribute to the development of GC. Further studies with larger sample size and functional experiments are needed to validate our findings.

Keywords: Helicobacter pylori; IL-11; gastric cancer; polymorphism.

Figure 1

Expression of IL-11 gene with development and prognosis of gastric cancer (GC). (A) The expression of the IL-11 gene in GC tissues (red) and adjacent normal tissues (black); (B) the expression of the IL-11 gene with overall survival of GC; (C) the expression of the IL-11 gene with first progression; (D) the expression of the IL-11 gene with post-progression survival.

Figure 2

mRNA expression correlation analysis of IL-11.