title: Effects of interleukin-10 polymorphisms, Helicobacter pylori infection, and smoking on the risk of noncardia gastric cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Epidemiology Branch, National Cancer Center, Goyang, Korea.
authors.forename: Jeongseon
authors.initials: J
authors.lastname: Kim
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Cho
authors.forename: Il Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Lee
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Cho
authors.forename: Myeong-Cherl
authors.initials: MC
authors.lastname: Kook
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Nam
authors.forename: Keun Won
authors.initials: KW
authors.lastname: Ryu
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics* / Q000382:microbiology
chemical_list: D016753:Interleukin-10