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The interferon gamma receptor 1 (IFNGR1) -56C/T gene polymorphism is associated with increased risk of early gastric carcinoma
  1. Paulo Canedo
  1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
    1. Giovanni Corso (corso5{at}unisi.it)
    1. Department of Human Pathology and Oncology, Surgical Oncology Unit, Translational Reserach Laborator, Italy
      1. Fabio Pereira (fabiop{at}ipatimup.pt)
      1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
        1. Nuno Lunet (nlunet{at}med.up.pt)
        1. Medical Faculty of Porto, Portugal
          1. Gianpaolo Suriano (gsuriano{at}ipatimup.pt)
          1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
            1. Ceu Figueiredo (cfigueiredo{at}ipatimup.pt)
            1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
              1. Corrado Pedrazzani (pedrazzani{at}unisi.it)
              1. Department of Human Pathology and Oncology, Surgical Oncology Unit, Translational Reserach Laborator, Italy
                1. Herculano Moreira (josem{at}iol.pt)
                1. Medical Faculty of Porto, Portugal
                  1. Henrique Barros (hbarros{at}med.up.pt)
                  1. Medical Faculty of Porto, Portugal
                    1. Fatima Carneiro (fcarneiro{at}ipatimup.pt)
                    1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
                      1. Raquel Seruca (rseruca{at}ipatimup.pt)
                      1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal
                        1. Franco Roviello (roviello{at}unisi.it)
                        1. Department of Human Pathology and Oncology, Surgical Oncology Unit, Translational Reserach Laborator, Italy
                          1. Jose Carlos Machado (josem{at}ipatimup.pt)
                          1. IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal

                            Abstract

                            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.

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