title: The interferon gamma receptor 1 (IFNGR1) -56C/T gene polymorphism is associated with increased risk of early gastric carcinoma.
abstract: OBJECTIVE
  It has been demonstrated that polymorphisms within inflammation-related genes are associated with the risk of gastric carcinoma (GC) in people infected with Helicobacter pylori. Recently, polymorphisms in the gene encoding the interferon gamma receptor 1 (IFNGR1) were found to be associated with increased susceptibility to H pylori infection. We aimed to determine the association between polymorphisms in the IFNGR1 gene and development of chronic gastritis and GC.
  
  
  METHODS
  In a case-control study including 733 controls, 213 patients with chronic gastritis and 393 patients with GC, the IFNGR1 -611*G/*A, -56*C/*T, +1004*A/*C and +1400*T/*C polymorphisms were genotyped. A second independent case-control study including 100 controls and 65 patients with GC was used for confirmation of the original results. The effect of the -56*C/*T promoter polymorphism in the level of expression of the IFNGR1 gene was evaluated by an IFNGR1 -56*C/*T allele specific luciferase reporter assay.
  
  
  RESULTS
  In patients with early onset GC (defined as being less than 40 years of age at the time of diagnosis) we found a significant over-representation of the IFNGR1 -56*T/*T homozygous genotype with an odds ratio (OR) of 4.1 (95% confidence interval (CI) 1.6 to 10.6). This result was confirmed in a second independent case-control study. In the luciferase reporter assay we observed a 10-fold increase (p<0.001) in luciferase expression associated with the IFNGR1-56*T allele.
  
  
  CONCLUSIONS
  Our results indicate that the IFNGR1 -56C/T polymorphism is a relevant host susceptibility factor for GC development. Our data also indicate that this genetic polymorphism is functionally relevant and may be related to the early development of GC.
authors.affiliation: IPATIMUP, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal.
authors.forename: P
authors.initials: P
authors.lastname: Canedo
authors.forename: G
authors.initials: G
authors.lastname: Corso
authors.forename: F
authors.initials: F
authors.lastname: Pereira
authors.forename: N
authors.initials: N
authors.lastname: Lunet
authors.forename: G
authors.initials: G
authors.lastname: Suriano
authors.forename: C
authors.initials: C
authors.lastname: Figueiredo
authors.forename: C
authors.initials: C
authors.lastname: Pedrazzani
authors.forename: H
authors.initials: H
authors.lastname: Moreira
authors.forename: H
authors.initials: H
authors.lastname: Barros
authors.forename: F
authors.initials: F
authors.lastname: Carneiro
authors.forename: R
authors.initials: R
authors.lastname: Seruca
authors.forename: F
authors.initials: F
authors.lastname: Roviello
authors.forename: J C
authors.initials: JC
authors.lastname: Machado
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005756:Gastritis / Q000382:microbiology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017471:Receptors, Interferon / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D000096743:Interferon gamma Receptor
chemical_list: D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor