Variation in proinflammatory and anti-inflammatory cytokine genes influence individual responses to carcinogenic exposures.
It has been found that polymorphisms in interleukin (IL)-1, and its endogenous receptor antagonist, are associated with a risk of Helicobacter pylori-related gastric cancer.
In this study, researchers from the United States and Scotland evaluated the role of proinflammatory cytokine gene polymorphisms in gastric and esophageal cancers.
The team assessed polymorphisms of the IL-1 gene cluster, and 4 other cytokine genes, in a population-based study of upper gastrointestinal cancers. Cancers included 126 gastric cardia and 188 noncardia adenocarcinoma, 53 esophageal squamous cell carcinoma, and 108 adenocarcinoma.
The study also included 212 frequency-matched controls.
|Proinflammatory genotypes were associated with an increased risk of noncardia gastric cancer.|
The researchers calculated odds ratios for the different cancers from logistic regression models which were adjusted for potential confounding factors.
The team found that proinflammatory genotypes of tumor necrosis factor and IL-10 were both associated with an increased risk of noncardia gastric cancer.
They determined that multiple proinflammatory polymorphisms of IL-1Bo IL-1 receptor antagonist, tumor necrosis factor A, and IL-10 conferred greatest risk. They calculated odds ratios of 2.8 for 1, 5.4 for 2, and 27.3 for 3 or 4 high-risk genotypes.
However, these polymorphisms were not found to be related to the risks of esophageal or gastric cardia cancers.
Furthermore, polymorphisms in IL-4 and IL-6 were not associated with any of the cancers studied.
Dr Emad El-Omar's team concluded, "A proinflammatory cytokine genetic profile increases the risk of noncardia gastric adenocarcinoma but not other upper gastrointestinal cancers".
"Possibly by inducing a hypochlorhydric and atrophic response to gastric H. pylori infection.