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Gastrointestinal Cancer

Interleukin 1-β gene polymorphisms and risk of gastric cancer in Sweden

, , , , , & show all
Pages 339-345 | Received 22 Sep 2008, Published online: 08 Jul 2009
 

Abstract

Objective. Helicobacter pylori (H. pylori) infection stimulates the production of interleukin (IL)-1β, a pro-inflammatory cytokine and suppressor of gastric acid secretion. As both inflammation and hypochlorhydria, which might facilitate proximal colonization of H. pylori and other bacterial species alike, have been implicated in gastric carcinogenesis, much attention has been directed to functional genetic polymorphisms that affect the production of IL-1β. The purpose of this study was to clarify the role of these polymorphisms. Material and methods. We analysed a population-based, case-control study in 5 Swedish counties and a hospital-based, case-control study conducted in 8 Swedish hospitals, with a total of 351 gastric cancer cases and 539 controls. The IL1B-31, IL1B-511 and IL1B+3954 biallelic polymorphisms were genotyped using pyrosequencing. The variable number of tandem repeats (VNTR) polymorphism of IL1-RN was analysed using polymerase chain reaction (PCR) followed by gel electrophoresis. Relative risks were estimated by odds ratios with 95% confidence intervals, derived from unconditional logistic regression. Results. The risk of gastric cancer was unrelated to genotype in all of the studied polymorphic loci, and the absence of any association was confirmed in both the population-based and hospital-based case-control studies. Analyses confined to histological subtypes (intestinal or diffuse) and site-specific tumours (cardia or distal stomach), as well as analyses stratified by H. pylori infection status and family history of gastric cancer, did not reveal any significant increases or decreases in risk. Conclusion. Our results do not lend support to the hypothesis that human genetic polymorphisms related to the production of IL-1β are associated with the risk of gastric cancer.

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