A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma.
OBJECTIVE
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.
Machado
José Carlos
JC
Institute of Molecular Pathology and Immunology of the University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal. josem@ipatimup.pt
Figueiredo
Céu
C
Canedo
Paulo
P
Pharoah
Paul
P
Carvalho
Ralph
R
Nabais
Sérgio
S
Castro Alves
Catarina
C
Campos
Maria Luisa
ML
Van Doorn
Leen-Jan
LJ
Caldas
Carlos
C
Seruca
Raquel
R
Carneiro
Fátima
F
Sobrinho-Simões
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D005757:Gastritis, Atrophic / Q000209:etiology* / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections / Q000145:classification / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D008875:Middle Aged; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D012306:Risk; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha