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The interferon gamma receptor 1 (IFNGR1) −56C/T gene polymorphism is associated with increased risk of early gastric carcinoma
  1. P Canedo1,2,
  2. G Corso3,
  3. F Pereira1,
  4. N Lunet4,
  5. G Suriano1,
  6. C Figueiredo1,2,
  7. C Pedrazzani3,
  8. H Moreira2,
  9. H Barros4,
  10. F Carneiro1,2,
  11. R Seruca1,2,
  12. F Roviello3,
  13. J C Machado1,2
  1. 1Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
  2. 2Faculty of Medicine, Porto, Portugal
  3. 3Department of Human Pathology and Oncology, Surgical Oncology Unit, University of Siena, Istituto Toscano Tumori, Siena, Italy
  4. 4Department of Hygiene and Epidemiology, Faculty of Medicine, Porto, Portugal
  1. Dr J C Machado, IPATIMUP, Rua Dr Roberto Frias, s/n, 4200-465 Porto, Portugal; josem{at}


Background and aim: 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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  • Funding: This work was supported by (1) Fundação para a Ciência e Tecnologia (REEQ/218/SAU/2005, POCTI/SAU-ESP/56126/2004 and POCTI/SAU-ESP/61685/2004); (2) Programa Operacional Ciência, Tecnologia e Inovação (POCTI), by Fundo Comunitário Europeu (FEDER); (3) Programa Operacional de Saúde/SAUDE XXI; (4) Associação Portuguesa da Industria Farmacêutica (APIFARMA); (5) the Sixth Research Framework Programme of the European Union, Project INCA (LSHC-CT-2005-018704); and (6) a grant from Istituto Toscano Tumori (ITT) Region of Tuscany, Italy.

  • Competing interests: None.

  • Ethics approval: Approval for this study was given by the Medical Faculty of Porto in October 2002.

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