A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma

• Type: Article in International Scientific Journal
• Date: 2003

Authors

Machado JC (Author) FMUP; Figueiredo C (Author) FMUP; Canedo, P (Author) Other; Pharoah, P (Author) Other; Carvalho, R (Author) Other; Nabais, S (Author) Other; Alves, CC (Author) Other; Campos, ML (Author) Other; Van Doorn, LJ (Author) Other; Caldas, C (Author) Other; Seruca, R (Author) FMUP; Carneiro F (Author) FMUP; Sobrinho Simoes, M (Author) FMUP

Journal

Title: Gastroenterology

Vol. 125

Pages: 364-371

ISSN: 0016-5085

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 396 Citations

Scopus - 443 Citations

Other information

Authenticus ID: P-000-FPD

DOI: 10.1016/s0016-5085(03)00899-0

Abstract (EN): Background & Aims: Pro-inflammatory polymorphisms within the genes interleukin (IL)-1B and IL-1RN are associated with risk for gastric carcinoma (GC) in Helicobacter pylori-infected individuals. We aimed to determine the association between variation of the tumor necrosis factor (TNF)-alpha gene and the risk for chronic atrophic gastritis (CAG) and GC. We also investigated the extent to which the combined effect of proinflammatory genetic polymorphisms (IL-1B, IL-1RN, and TNF-alpha), and the combined effect of TNF-alpha and bacterial genotypes each influence such a risk. Methods: In a case-control study including 306 controls, 221 individuals with chronic gastritis, and 287 GC patients, the TNF-alpha-308 and IL-1B-511 bi-allelic polymorphisms, the IL-1RN variable number of tandem repeats (VNTR), and the H. pylori genes vacA (s and m regions) and cagA were genotyped. Results: We found that carriers of the TNF-alpha-308*A allele are at increased risk for GC development with an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.3-2.7). For both CAG and GC, the odds of developing disease increased with the number of high-risk genotypes. Individuals carrying high-risk genotypes at the 3 loci are at increased risk for CAG and GC with an OR of 5.8 (95% CI, 1.1-31.0) and 9.7 (95% CI, 2.6-36.0), respectively. The risk for GC was not affected significantly by the combination of bacterial and TNF-alpha-308 genotypes. Conclusions: These findings show that a proinflammatory polymorphism in the TNF-alpha gene is associated with increased risk for GC, and that it is possible to define a specific genetic profile associated with highest risk for CAG and GC.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8