© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 22, 1680-1687,
November 20, 2002
© 2002 Oxford University Press
ARTICLE |
Helicobacter pylori and Interleukin 1 Genotyping: An Opportunity to Identify High-Risk Individuals for Gastric Carcinoma
C. Figueiredo, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal, and Delft Diagnostic Laboratory, Delft, The Netherlands; J. C. Machado, R. Seruca, IPATIMUP, and Faculty of Medicine, University of Porto, Porto; P. Pharoah (Departments of Oncology and Public Health), C. Caldas (Department of Oncology), University of Cambridge, Cambridge, U.K.; S. Sousa, R. Carvalho, IPATIMUP, Porto; A. F. Capelinha, Hospital S. João, Porto; W. Quint, L.-J. van Doorn, Delft Diagnostic Laboratory, Delft; F. Carneiro, M. Sobrinho-Simões, IPATIMUP, Porto, Faculty of Medicine, Porto, and Hospital S. João, Porto.
Correspondence to: Céu Figueiredo, Ph.D., IPATIMUP, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal (e-mail: cfigueiredo{at}ipatimup.pt).
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). Conclusion: Combined bacterial/host genotyping may provide an important tool in defining disease risk and targeting H. pylori eradication to high-risk individuals.
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