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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2003

Autores

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

Revista

Título: Gastroenterology

Vol. 125

Páginas: 364-371

ISSN: 0016-5085

Editora: Elsevier

Indexação

ISI Web of Knowledge - 396 Citações

Scopus - 443 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8