Interleukin-1B gene promoter variants are associated with an increased risk of gastric cancer in a Chinese population
白细胞介素-1B基因启动子变异与中国人群患胃癌的风险增加有关

Helicobacter pylori is a significant human pathogen of the stomach's epithelial lining. This type of carcinogen is associated with gastric cancer, indigestion, peptic ulcers, and upper digestive diseases. Therefore, successful treatment and eradication of this bacterium are required to reduce the prevalence of these diseases, especially in high-risk individuals. Moreover, some concerns exist regarding the extensive use of elimination therapy, such as anti-microbial resistance and rising H. pylori-associated diseases. Since there is still no effective vaccine, finding alternative therapies would appear to be a worthwhile pursuit. In this regard, curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.

Interleukin-1 (IL-1) is a pro-inflammatory cytokine which may be related to urolithiasis. Genetic polymorphisms of the interleukin-1beta (IL-1β) have been proposed as markers for urolithiasis in some areas. Due to the high incidence of urolithiasis in Uighur children (Xinjiang, China) and existence of ethnic difference, our aim is to explore the potential of IL-1 gene polymorphisms and urolithiasis among these children.

Genomic DNA extracted from peripheral blood of 115 patients and 98 controls were used for genotype polymorphisms analyses. IL-1 receptor antagonist (IL-1RN) gene variable number of tandem repeat (VNTR) gene polymorphisms were analyzed by PCR method. PCR-based restriction analysis was done for the IL-1β (−511) and IL-1β (+3954) gene polymorphisms by endonucleases Ava I and Taq I, respectively. The genotype distribution, allele frequencies, carriage rate, and haplotype frequencies were statistically analyzed.

No significant differences were observed in genotypic frequencies between pediatric urolithiasis patients and control group for IL-1RN gene (χ²=1.906, p=0.605), IL-1β (−511) gene (χ²=0.105, p=0.949), or IL-1β (+3954) gene (χ²=3.635, p=0.169). There were yet no significant differences of the allele frequencies of IL-1RN VNTR gene (p=0.779), IL-1β (−511) gene (p=0.941), and IL-1β (+3954) gene (p=0.418) in the case and control groups, as well as the carriage rate and haplotype of them (all p>0.05).

The associations between IL-1RN VNTR, IL-1β (−511) and IL-1β (+3954) genes polymorphisms and urolithiasis were not significant in Uighur children. The results need to be confirmed in studies with larger population sample size, as well as in other ethnic groups.

To clarify the impact of IL-1B gene polymorphisms (IL-1B–511C/T, IL-1B–31C/T, IL-1B+3954C/T) in Helicobacter pylori (H. pylori) infection by mean of a meta-analysis.

The relevant studies were retrieved from PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases until September 9, 2018. Odds ratio (OR) and its 95% confidence intervals (CIs) were used to assess the associations. Statistical analyses of this meta-analysis were conducted by using STATA 12 software.

Totally, 45 articles including 9606 cases and 5654 controls were enrolled in this meta-analysis. Our results indicated that IL-1B–511C/T polymorphism was significantly related to an increased the risk of H. pylori infection under recessive model (OR = 1.13, 95% CI: 1.00–1.27, P = 0.048). However, no significant associations were obtained between H. pylori infection and IL-1B–31C/T as well as IL-1B+3954C/T polymorphisms under all models. In addition, subgroup analyses were also performed by country, study design, and detection methods of H. pylori.

This meta-analysis suggested that IL-1B–511C/T polymorphism was related to the risk of H. pylori infection. Further larger studies with high quality are needed to conform these findings.

Despite advancement in screening and early diagnosis, gastrointestinal cancers continue to be a leading cause of death worldwide. The advances in molecular biology approaches have led us to identify new potential drug targets. However, the overall success rate of drugs during clinical development remains lower than expected. Since mouse models play a pivotal role in preclinical research, efficient use of various animal models can accelerate the drug development pipeline with more predictive in vivo results. In this chapter we will describe the role of various mouse models in understanding the pathogenesis of various malignancies specifically colorectal cancer, pancreatic cancers, and stomach cancer. Further, we will describe orthotopic transplant models, organoid xenografts, patient-derived tumor xenografts, and their potential role in drug discovery.

Host genetic factors that control the production of cytokines, including interleukin-1β (IL-1β), possibly affect susceptibility to many Helicobacter pylori-related diseases. There is a complex interplay between H. pylori infection, the subsequent production of certain cytokines, and H. pylori-related diseases. We conducted a meta-analysis to clarify the association between the IL1B −31C > T polymorphism and H. pylori infection, and possible subsequent pathogenic mechanisms.

Published literature contained within PubMed, Embase, and the Cochrane Library was used in our meta-analysis. Data were analyzed with the STATA 13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (95% CI). Egger's regression test, Begg's rank correlation test, and Begg's funnel plot were used to test publication bias.

A total of 12 case–control studies comprising 5827 subjects (3335 cases and 2492 controls) were available for our meta-analysis. The IL1B −31C > T polymorphism was associated with an increased risk of H. pylori infection in Asian and Latin American population (TT + CT vs. CC, OR = 1.29, 95% CI = 1.14–1.46; TT vs. CT + CC, OR = 1.23, 95% CI = 1.09–1.39; TT vs. CC, OR = 1.43, 95% CI = 1.22–1.67; T allele vs. C allele, OR = 1.19, 95% CI = 1.10–1.29). A significant association was also found for all genetic models in various subgroups (cancer and no-cancer, hospital- and population-based).

Our meta-analysis demonstrated that IL1B −31C > T polymorphism might increase H. pylori infection risk in Asian and Latin American population. Further studies with different ethnicities and larger sample size are required to validate this result.

Interleukin-1β (Il1b) is considered to be involved in Helicobacter pylori (HP)-induced human gastric carcinogenesis, while the role of its polymorphisms in gastric cancer susceptibility remains controversial. Here, we aimed to clarify the role of HP infection-induced IL1B in gastric inflammation and carcinogenesis using Il1b^−/− (Il1b-null) mice. In gastric mucosa of the Il1b^+/+ (WT) mice, HP infection induced Il1b expression and severe inflammation. In contrast, in Il1b-null mice, recruitment of neutrophils and macrophages by HP infection was markedly suppressed. In a carcinogenicity test, the multiplicity of gastric tumors was significantly suppressed in theIl1b-null mice (58% of WT; P < 0.005). Mechanistically, HP infection induced NF-κB activation both in the inflammatory and epithelial cells in gastric mucosae, and the activation was attenuated in the Il1b-null mice. Accordingly, increased proliferation and decreased apoptosis of gastric epithelial cells induced by HP infection in the WT mice were attenuated in the Il1b-null mice. These results demonstrated that the IL1B physiologically induced by HP infection enhanced gastric carcinogenesis by affecting both inflammatory and epithelial cells.