Article

Effects of interleukin-10 polymorphisms, Helicobacter pylori infection, and smoking on the risk of noncardia gastric cancer.

Cancer Epidemiology Branch, National Cancer Center, Goyang, Korea.
PLoS ONE (impact factor: 4.09). 01/2012; 7(1):e29643. DOI:10.1371/journal.pone.0029643
Source: PubMed

ABSTRACT Both 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.
We 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.
The 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).
Inflammation-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.

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Keywords

age-matched healthy controls
 
case-control study
 
complete linkage disequilibrium
 
gastric carcinogenesis
 
H. pylori
 
H. pylori infection
 
H. pylori-negative nonsmokers homozygous
 
H. pylori-positive smokers
 
H. pylori-positive subjects
 
Helicobacter pylori
 
IL10 polymorphisms
 
increased risk
 
Inflammation-related genetic variants
 
intestinal-type gastric cancer
 
intestinal-type noncardia gastric cancer
 
Multiple logistic regression models
 
noncardia gastric cancer
 
noncardia gastric carcinogenesis
 
statistically significant interaction
 
three IL10 polymorphisms