Further, meta-analysis revealed significant association of IL-1βrs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18-14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48-20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori .
The pro-inflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors, and polymorphisms in the IL-1 gene cluster resulting in increased IL-1β production have been associated with increased risk for gastric cancer.
Subgroup analysis showed a significant correlation between IL-1β-511C/T polymorphism and susceptibility to gastric cancer in residents of southern China and in patients with intestinal-type gastric cancer, but not in residents of northern China or in patients with diffuse gastric cancer.
Furthermore, H. pylori infection has a synergistic effect on the development of GC with IL-1β gene polymorphisms, and the highest prevalence of severe gastric abnormalities are found in patients with both host and bacterial high-risk genotypes (cagA(+)/vacAs1(+)/IL-1β-511T).
These results suggested that SNPs in the IL-1 family genes play important roles in the development of GC and the IL-1F5 might be the target gene of miR-197, and miR-197 might negatively regulate its expression.
The proinflammatory cytokine IL-1β plays a crucial role in the development of gastric tumors and polymorphisms in the IL-1 gene cluster leading to increased IL-1β production have been associated with increased risk for gastric cancer.
Our results demonstrated that the IL-1β -511 C/C and IL-1β-511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03).
In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05).
These findings suggest that the IL1B-511T/T allele is associated with enhanced hypermethylation of multiple CpG island loci, which might contribute to an increase in the risk for gastric cancer in individuals with H. pylori infection and IL1B-511T/T allele.
The distribution of the four major IL1B variants (IL1B-3737C>T, -1464G>C, - 511C>T, -31T>C) were analyzed in 116 and 142 patients with gastric cancer and 'high risk gastritis', respectively, as well as 94 healthy controls.
Multivariate regression analysis showed that cagE, babA2, and IL-1RN-1/2 genotypes were independent predictors of GC, but when patients with benign disorders were grouped together (NUD + DU) and compared with patients with GC, regression analysis disclosed that babA2 (P = 0.000) and IL-1B-31 gene polymorphisms (CC or CT) (P = 0.01) were the only independent markers of GC.
It has been reported that interleukin-1beta (IL-1B) genes play a crucial role in the genetic predisposition to gastric cancer although there is no information about their role in different subtypes of gastric cancer.