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  • Title: The interferon gamma receptor 1 (IFNGR1) -56C/T gene polymorphism is associated with increased risk of early gastric carcinoma.
    Author: Canedo P, Corso G, Pereira F, Lunet N, Suriano G, Figueiredo C, Pedrazzani C, Moreira H, Barros H, Carneiro F, Seruca R, Roviello F, Machado JC.
    Journal: Gut; 2008 Nov; 57(11):1504-8. PubMed ID: 18593809.
    Abstract:
    BACKGROUND AND AIMS: 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.
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