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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. 1
    Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
  2. 2
    Faculty of Medicine, Porto, Portugal
  3. 3
    Department of Human Pathology and Oncology, Surgical Oncology Unit, University of Siena, Istituto Toscano Tumori, Siena, Italy
  4. 4
    Department 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}ipatimup.pt

Abstract

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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Footnotes

  • 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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