Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma.
BACKGROUND
Both Helicobacter pylori genotype and host genetic polymorphisms play a role in determining the clinical consequences of H. pylori infection. We investigated whether there are any combinations of bacterial and host genotypes that are particularly associated with the occurrence of gastric carcinoma.


METHODS
Genotypic variations in virulence-associated genes of H. pylori vacA (s and m regions) and cagA were determined in 221 subjects with chronic gastritis and 222 patients with gastric carcinoma by polymerase chain reaction (PCR)-line probe assay. Polymorphisms in the human interleukin 1 beta (IL-1B) gene (IL-1B-511*C or IL-1B-511*T) and in the IL-1 receptor antagonist gene (IL-1RN intron 2 variable number of tandem repeats) were evaluated by PCR and single-strand conformation polymorphism analysis. All statistical tests were two-sided.


RESULTS
Infection with vacAs1-, vacAm1-, and cagA-positive strains of H. pylori was associated with an increased risk for gastric carcinoma, with odds ratios (ORs) of 17 (95% confidence interval [CI] = 7.8 to 38), 6.7 (95% CI = 3.6 to 12), and 15 (95% CI = 7.4 to 29), respectively. IL-1B-511*T carriers (IL-1B-511*T/*T or IL-1B-511*T/*C) homozygous for the short allele of IL-1RN (IL-1RN*2/*2) had an increased gastric carcinoma risk (OR = 3.3, 95% CI = 1.3 to 8.2). For each combination of bacterial/host genotype, the odds of having gastric carcinoma were greatest in those with both bacterial and host high-risk genotypes: vacAs1/IL-1B-511*T carrier (OR = 87, 95% CI = 11 to 679), vacAm1/IL-1B-511*T carrier (OR = 7.4, 95% CI = 3.2 to 17), cagA-positive/IL-1B-511*T carrier (OR = 25, 95% CI = 8.2 to 77), vacAs1/IL-1RN*2/*2 (OR = 32, 95% CI = 7.8 to 134), vacAm1/IL-1RN*2/*2 (OR = 8.8, 95% CI = 2.2 to 35), and cagA-positive/IL-1RN*2/*2 (OR = 23, 95% CI = 7.0 to 72).


CONCLUSIONS
Combined bacterial/host genotyping may provide an important tool in defining disease risk and targeting H. pylori eradication to high-risk individuals.
Figueiredo
Céu
C
C. Figueiredo, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal. cfigueiredo@ipatimup.pt
Machado
José Carlos
JC
Pharoah
Paul
P
Seruca
Raquel
R
Sousa
Sónia
S
Carvalho
Ralph
R
Capelinha
Ana Filipa
AF
Quint
Wim
W
Caldas
Carlos
C
van Doorn
Leen-Jan
LJ
Carneiro
Fátima
F
Sobrinho-Simões
Manuel
M
D000328:Adult; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000382:microbiology; D002908:Chronic Disease; D016001:Confidence Intervals; D005260:Female; D005756:Gastritis / Q000235:genetics / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000382:microbiology; D008875:Middle Aged; D018598:Minisatellite Repeats; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007375:Interleukin-1; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori