Background and aim: It was demonstrated that polymorphisms within inflammation-related genes are associated with risk of gastric carcinoma (GC) in Helicobacter pylori-infected individuals. 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 individuals with chronic gastritis and 393 GC patients, 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 GC patients 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 individuals with early onset GC (defined as having 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] 1.6-10.6). 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 with early development of GC.