Relevance of Helicobacter pylori virulence genes and interleukin-1 polymorphisms for the development of atrophy and gastric carcinoma

Leen-Jan van Doorna, Céu Figueiredoa,b, José Carlos Machadob, Raquel Serucab, Sónia Sousab, Ralph Carvalhob, Carlos Caldasc, Wim Quinta, Fátima Carneirob,d, Manuel Sobrinho-Simõesb,d

a Delft Diagnostic Laboratory, Delft, The Netherlands; bIPATIMUP, Porto, Portugal; c Department of Oncology, University of Cambridge, Cambridge, United Kingdom, d Faculty of Medicine, Porto, Portugal.

Helicobacter pylori infection causes severe gastrointestinal disease in only a subset of individuals. This may be related to both human genetic polymorphisms and bacterial genotypes. Our aimwas to assess the relevance of human IL-1 polymorphisms as well as H. pylori vacA, and cagA genotypes in a population of Portuguese patients. A total of 443 subjects diagnosed with chronic superficial gastritis, atrophy or gastric carcinoma were studied. Gastric biopsy specimens were histologically examined and classified. H. pylori vacA and cagA genes and human IL-1B and IL-1RN genes were directly genotyped in the gastric specimens by PCR-based methods. Patients infected with more virulent H. pylori genotypes (vacAs1, vacA m1, cagA+) showed more severe gastritis, and these strains were associated with an increased risk for gastric carcinoma. Also, IL-1B -511 T carriers and IL-1RN *2 homozygotes were associated with more severe gastritis, and an increased risk for gastric carcinoma. When combining the H. pylori virulence genotypes with the IL1 polymorphisms, odds ratios increased for both atrophy and gastric carcinoma, suggesting a synergistic effect. Human IL1 polymorphisms as well as H. pylori vacA and cagA genotypes are significantly associated with histological parameters as well as with an increased risk for gastric carcinoma. Specific bacterial virulence factors and host genetic susceptibility markers may have a synergistic effect, enhancing the risk for gastric pathology, indicating that genetic variability of the host as well as the infectious organism are clinically relevant. These findings may explain why only some individuals infected with H. pylori develop serious gastric pathology.

KEY WORDS: gastric cancer, PCR genotyping, atrophy, IL1 typing.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Risk Assessment, Part 1.