Association between pro-inflammatory cytokine gene polymorphism and increased risk gastric cancer

Interleukin -1beta (IL-1beta) is a pro-informmatory cytokine with multiple biological effects and is synthesized during microbial infection including Helicobacter pylori (Hp) infection with a local increase of IL-1beta expression in the gastric mucosa. Genetic variations in IL-1beta which enhances its production, and its endogenous receptor antagonist (IL-IRN), are associated with increased risk of Hp-associated gastric cancer (GC) development. Polymorphisms such as C/T at - 31 position in IL-1β promoter region harboring the type 2 genotype of IL-IRN are the most important genetic variations in IL-1 gene cluster which is associated with GC occurrence in Hp-infected patients. Molecular genetic studies have shown that carriers of IL-1β-31T have an increased risk of developing gastric cancer with no difference between homozygote and heterozygote individuals. In contrast among different genotypes of IL-IRN, possession of allele2 in mostly associated with an increased risk of GC in homozygote but not in heterozygote. GC cases (n=51) and non GC dyspeptic controls (n=104) were enrolled into this study. Polymorphisms of IL-1beta and IL1-ra were investigated via PCR-CTPP (PCR with Confronting Two-Pair Primers).Host factors were extracted from patient questionnaires and statistical cross tab analusis was performed. Diversity of IL-1β-31T polymorpgisms among GC samples was: 19/6% TT, 66.7% CT and 13.7% CC, and for non GC samples: 28.6% TT, 55.1% CT and 16.3% CC. Frequency of allele 2 IL-1ra in GC and non- GC samples are 64.4% and 7.3% respectively. In this study, there was an associaion founf between blood group distribution and different IL-IRN genotypes (p=0.021). The other factors are similarly distributed among different genotypes of IL-1β-31T and IL-IRN.

کلیدواژه ها:

H. pylori ، pro-inflammatory cytokines ، IL-1beta ، polymorphism ، IL-1ra ، gastric cancer