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

Gastroenterology. 2003 Aug;125(2):364-71. doi: 10.1016/s0016-5085(03)00899-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*


  • Interleukin-1
  • Tumor Necrosis Factor-alpha