Combined polymorphism analysis of glutathione S-transferase M1/G1 and interleukin-1B (IL-1B)/interleukin 1-receptor antagonist (IL-1RN) and gastric cancer risk in an Omani Arab Population

Abstract

Background: Host genetics have been implicated in gastric cancer carcinogenesis. Polymorphisms of glutathione S-transferase (GST) M1 and G1 and of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) were shown to increase gastric cancer predisposition in several studies. To our knowledge, this is the first report on the combined analysis of polymorphisms GSTM1/G1 and IL-1B/IL-1RN genes in gastric adenocarcinoma.

Methods: Genomic DNA was extracted from peripheral blood of 107 control subjects and 107 gastric cancer patients. Analysis for the GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction. The DNA samples were analyzed using the TaqMan allelic discrimination test for the polymorphism of IL-1B at positions-31. The variable number of tandem repeats of IL-1RN was genotyped using polymerase chain reaction followed by agarose gel electrophoresis.

Results: There were no statistically significant associations between the GSTM1/G1 or IL-1B-31 genes and gastric cancer risk. There was a statistical association between the presence of the IL-1RN*2 allele and gastric cancer (odds ratio 2.2, 95% confidence interval=1.2-3.7, P=0.01). Combined analysis showed that a combination of the null GSTM1 genotype and carriers of IL-1RN*2 was associated with a statistically significant correlation with gastric cancer (odds ratio=3.6, 95% confidence interval=1.4-9.4, P=0.008).

Conclusions: The current study suggests that the individual variation in both the cellular inflammatory modulator IL-1RN and the antioxidative property of GSTM1 may predispose individuals to an increased risk of gastric cancer.