The interferon gamma receptor 1 (IFNGR1)-56C/T gene polymorphism is associated with increased risk of early gastric carcinoma

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Canedo P (Author) Other; Corso G (Author) Other; Pereira F (Author) Other; Lunet N (Author) FMUP; Suriano G (Author) Other; Figueiredo C (Author) FMUP; Pedrazzani C (Author) Other; Moreira H (Author) Other; Barros H (Author) FMUP; Carneiro F (Author) FMUP; Seruca R (Author) FMUP; Roviello F (Author) Other; Machado JC (Author) FMUP

Journal

Title: Gut

Vol. 57 No. 11

Pages: 1504-1508

ISSN: 0017-5749

Publisher: BMJ PUBLISHING GROUP

Indexing

ISI Web of Knowledge - 43 Citations

Scopus - 39 Citations

Other information

Authenticus ID: P-003-V4H

DOI: 10.1136/gut.2007.143578

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5