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Allele 2 of the Interleukin-1 Receptor Antagonist Gene Is Associated With Early Gastric Cancer

From the Medizinische Poliklinik, Chirurgische Klinik und Poliklinik, Klinikum der Universität München, Standort Innenstadt; Labor für Immungenetik, Kinderklinik und Kinderpoliklinik, Klinikum der Universität München, Standort Innenstadt; Chirurgische Klinik und Poliklinik, Klinikum der Universität München, Standort Großhadern, München; Institut für Pathologie, Klinikum Bayreuth, Bayreuth, Germany

Address reprint requests to Christian Folwaczny, MD, PhD, Medizinische Poliklinik, Chirurgische Klinik und Poliklinik, Klinikum der Universität München, Nußbaumstraße 20, D-80336 München, Germany; e-mail: Christian.Folwaczny{at}medinn.med.uni-muenchen.de

PURPOSE: In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined.

PATIENTS AND METHODS: Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the ² test and the Fisher's exact test, respectively.

RESULTS: The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A–308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1ß and TNF-, could also be demonstrated.

CONCLUSION: The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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