Journal
GUT
Volume 57, Issue 11, Pages 1504-1508Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/gut.2007.143578
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Funding
- Fundacao para a Ciencia e Tecnologia [REEQ/218/SAU/2005, POCTI/SAU-ESP/56126/2004, POCTI/SAU-ESP/61685/2004]
- Programa Operacional Ciencia, Tecnologia e Inovacao ( POCTI)
- Fundo Comunitario Europeu
- Programa Operacional de Saude/SAUDE XXI
- Associacao Portuguesa da Industria Farmaceutica ( APIFARMA)
- Sixth Research Framework Programme of the European Union [LSHC-CT-2005-018704]
- Istituto Toscano Tumori ( ITT) Region of Tuscany, Italy
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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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