Interleukin‐1B 31 C>T polymorphism combined with Helicobacter pylori‐modified gastric cancer susceptibility: evidence from 37 studies

Abstract

Gastric cancer is one of the most common malignancies worldwide. Interleukin‐1‐beta (IL‐1β) is a pro‐inflammatory cytokine and potent inhibitor of gastric acid secretion. Some studies provided evidence of the association between IL‐1B 31 polymorphism and gastric cancer risk while other studies did not. Therefore, we conducted a comprehensive meta‐analysis to reassess the association. A systematic literature search of the PubMed and EMBASE databases identified 37 studies with 6108 cases and 8980 controls for this meta‐analysis. The crude odd ratios (ORs) and the 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Meta‐regression was used to determine the major source of heterogeneity across the studies. The pooled analysis did not suggest the significant association of IL‐1B 31 C>T polymorphism with gastric cancer risk. Stratified analysis was performed by ethnicity, source of control, genotype method, and indicated a significantly increased gastric cancer risk associated with IL‐1B 31T variant in the population‐based subgroup (heterozygous model: OR = 1.22, 95% CI = 1.03–1.45). Moreover, stratified analysis by Helicobacter pylori infection status indicated that IL‐1B 31 polymorphism increased gastric cancer risk in infection‐positive subgroup (homozygous model: OR = 1.35, 95% CI = 1.02–1.78; heterozygous model: OR = 1.31, 95% CI = 1.04–1.66; recessive model: OR = 1.29, 95% CI = 1.04–1.61). The study suggested that IL‐1B 31 polymorphism might confer susceptibility to gastric cancer in the presence of H. pylori infection, indicating a gene–environment interaction in gastric carcinogenesis.

Interaction Between Helicobacter Pylori and Host Genetic Variants in Gastric Carcinogenesis

“…This conclusion should be updated as this meta-analysis only included studies from 1990 to 2006, and many studies have been published since then [25,28,[35][36][40][41][42][43][44][45][46][47][48][49][50]. A very recent meta-analysis reported similar correlation where the T/T genotype of IL-1β-31 increased GC risk only in individuals with H. pylori infection (table 1) [51]. A meta-analysis of IL-1β-551C/T included 45 studies and showed that the T/T genotype could evaluate GC risk in subjects with H. pylori infection (OR: 1.70; 95% CI: 1.03-2.80; I 2 = 85%) (table 1) [52].…”

The “Janus Face” of Platelets in Cancer

“…It is unclear how IL-1β can induce thrombocytopenia in solid tumors, but it is known that -31 T > C SNP can increase susceptibility to thrombocytopenia in these malignancies [72]. A strong association between IL-1β -31 T > C SNP and Helicobacter pylori infection has also been reported: The two phenomena collaborate themselves to increase the risk of gastric cancer with hemorrhagic complications [75,76]. IL-6 is also involved in thrombocytopenic mechanisms, as well as in paraneoplastic thrombocytosis.…”

Pathogenesis of Helicobacter pylori infection

“…Numerous studies using single-nucleotide polymorphisms (SNPs) as genomic markers have identified novel links to H. pylori susceptibility and gastric cancer. 40 Recently, the meta-analysis of 37 studies performed by Ying et al 41 suggests that the IL-1β 31 C>T polymorphism confers susceptibility to gastric cancer when stratified by H. pylori infection status. This implicates IL-1β as a potent inhibitor of gastric acid secretion, thus favoring H. pylori colonization.…”