Interleukin 1-beta gene polymorphisms and risk of gastric cancer in Sweden.
OBJECTIVE
Helicobacter pylori (H. pylori) infection stimulates the production of interleukin (IL)-1 beta, 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-1 beta. The purpose of this study was to clarify the role of these polymorphisms.


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.


CONCLUSIONS
Our results do not lend support to the hypothesis that human genetic polymorphisms related to the production of IL-1 beta are associated with the risk of gastric cancer.
Persson
Christina
C
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Christina.Persson@ki.se
Engstrand
Lars
L
Nyrén
Olof
O
Hansson
Lars-Erik
LE
Enroth
Helena
H
Ekström
Anna-Mia
AM
Ye
Weimin
W
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology
D007375:Interleukin-1