The association between the interleukin-1 polymorphisms and gastric cancer risk depends on the family history of gastric carcinoma in the study population.

OBJECTIVES

The association between interleukin-1 polymorphisms, H. pylori and increased gastric cancer risk remains controversial.

AIMS: To compare the prevalence of these polymorphisms in individuals with two mutually exclusive diseases connected with infection, gastric cancer, and duodenal ulcer.

METHODS

121 gastric cancer and 119 duodenal ulcer patients. Genomic DNA was typed for polymorphisms at position -511, -31 in the interleukin-1beta gene (IL-1 beta) using primer extension and mass-spectrometry. Analysis of the variable number of tandem repeats in intron 2, in its receptor antagonist gene (IL-1RN) was performed by PCR and agarose gel electrophoresis.

RESULTS

All subjects were successfully genotyped for the three gene loci. IL-1 beta-511 was found to be in reverse linkage disequilibrium with IL-1 beta-31. The differences between gastric cancer and duodenal ulcer patients concerned only heterozygous variant of IL-1beta and were related to family history of gastric cancer, tumor stage, histology, site. Thus, CT carriers were found to have a higher risk of sporadic [OR 2.21 (95% CI, 1.22-3.99)], early [OR 2.81 (95% CI, 1.14-6.93)], diffuse [OR 2.48, (95% CI 1.21-5.09)] or non-cardia gastric cancer [OR 1.88 (95% CI 1.06-3.33)]. Furthermore, CT genotype was significantly more prevalent in gastric cancer patients with negative than in those with a positive family history (p = 0.039).

CONCLUSIONS

The association between the interleukin-1 polymorphisms and gastric cancer risk depends on the family history of gastric carcinoma in the study population. This phenomenon may be in part responsible for differences in results of interleukin-1 studies performed on populations with low and high gastric cancer prevalence.