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Interleukin-1 polymorphisms associated with increased risk of gastric cancer

A Correction to this article was published on 05 July 2001


Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease1. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion2, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy3, which are presumptive precursors of gastric cancer4. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA–protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine5 and a powerful inhibitor of gastric acid secretion6,7. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do not.

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Figure 1: Differential binding patterns between the T- and C-bearing alleles of the IL-1B promoter.


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We thank A. Goldstein and N. Chatterjee for advice on genetic and statistical issues, N. Dunlap for technical assistance, D. Gillen for help with subject recruitment and J. Goedert for suggestions. E.M.E. received a European Helicobacter pylori Study Group Research Fellowship from the Digestive Disorders Foundation, UK. This project was partly funded by the National Cancer Institute, National Institutes of Health, USA.

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El-Omar, E., Carrington, M., Chow, WH. et al. Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404, 398–402 (2000).

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