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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.

SUBMITTER: Liao C

PROVIDER: S-EPMC6751226 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Contribution of interaction between genetic variants of interleukin-11 and <i>Helicobacter pylori</i> infection to the susceptibility of gastric cancer.

Liao Chuanwen C Hu Shuqin S Zheng Zihan Z Tong Huazhang H

OncoTargets and therapy 20190911

<h4>Background</h4>Gastric cancer (GC) ranks the second leading cause of cancer-related mortality worldwide. We aimed to clarify the relevance of genetic variants of <i>IL-11</i>, a hub of various carcinogenic pathways, as well as their interactions with <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection in the development of GC.<h4>Methods</h4>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 D ...[more]

PMID: 31686851

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Project description:ObjectiveBoth variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans.MethodsWe genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer.ResultsThe IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction ?=?0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI] ?=?17.76 [6.17-51.06]) or the -592C (OR [95% CI] ?=?8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction ?=?0.080).ConclusionsInflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer.

Dataset Information

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

Publications

Contribution of interaction between genetic variants of interleukin-11 and <i>Helicobacter pylori</i> infection to the susceptibility of gastric cancer.

Similar Datasets

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