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

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 125; no. 2; p. 364
• Main Authors: Machado, José Carlos, Figueiredo, Céu, Canedo, Paulo, Pharoah, Paul, Carvalho, Ralph, Nabais, Sérgio, Castro Alves, Catarina, Campos, Maria Luisa, Van Doorn, Leen-Jan, Caldas, Carlos, Seruca, Raquel, Carneiro, Fátima, Sobrinho-Simões, Manuel
• Format: Journal Article
• Language: English
• Published: United States 01.08.2003
• Subjects: Adult; Aged; Aged, 80 and over; Chronic Disease; Gastritis, Atrophic - etiology; Gastritis, Atrophic - genetics; Genotype; Helicobacter Infections - classification; Helicobacter Infections - complications; Helicobacter pylori; Humans; Interleukin-1 - genetics; Middle Aged; Minisatellite Repeats; Polymorphism, Genetic; Risk; Stomach Neoplasms - etiology; Stomach Neoplasms - genetics; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0016-5085
• DOI: 10.1016/s0016-5085(03)00899-0

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. 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. 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. 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.