The roles of IL-6, IL-8 and IL-10 gene polymorphisms in gastric cancer: A meta-analysis
Introduction
Gastric cancer is the most frequently seen malignancy of digestive tract and the leading cause of cancer-related death all over the world [1]. In spite of enormous advances in pharmacotherapy and surgical treatment over the recent decades, gastric cancer remains one of the major threats to public health worldwide, and its 5-year relative survival rate is still no more than thirty percent [2]. To date, the etiology of gastric cancer is still ambiguous. However, abundant evidence supports that genetic predisposition to gastric cancer is crucial for its development. To begin with, numerous genetic variations have been verified to be correlated with an increased risk of gastric cancer by past epidemiological studies [3], [4], [5]. Additionally, family aggregation of gastric cancer is not uncommon, and positive family history, especially in first-degree relatives, has been proved to be a strong independent risk factor of gastric cancer [6]. Overall, these findings jointly indicate that genetic factors play an important part in the occurrence and development of gastric cancer.
Previous studies have shown that immune dysfunction is also implicated in the development of gastric cancer. In the first place, it was found that suppressor T cells are increased while cytotoxic T cells are decreased in patients with gastric cancer [7]. In the second place, some pilot studies have demonstrated that immune-stimulatory therapy could achieve disease regression and prolonged survival in gastric cancer patients [8], [9]. Consequently, certain polymorphisms of potent immune regulators, which are able to modulate anti-tumor immune responses, were thought to ideal genetic biomarkers of gastric cancer.
Recently, many genetic association studies have been conducted to investigate the potential roles of interleukin-6 (IL-6), IL-8, and IL-10 gene polymorphisms in gastric cancer, but the results of these studies were inconsistent and the sample size of each individual study is insufficient to draw a definite conclusion [10], [11], [12], [13]. Therefore, we performed this meta-analysis to better assess the potential correlations between these interleukin gene polymorphisms and the risk of gastric cancer.
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Literature search and inclusion criteria
This meta-analysis was complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement [14]. Potentially relevant articles were searched in PubMed, Medline, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) using the following keywords: “Interleukin-6”, “IL-6”, “Interleukin 6”, “IL 6”, “Interleukin-8”, “IL-8”, “Interleukin 8”, “IL 8”, “Interleukin-10”, “IL-10”, “Interleukin 10”, “IL 10”, “polymorphism”, “variant”, “mutation”,
Characteristics of included studies
Our systematic literature search identified 691 articles. After exclusion of irrelevant or duplicate articles by reading titles and abstracts, 141 potentially relevant articles were retrieved for further evaluation. Another 68 articles were subsequently excluded after reading the full text. Finally, a total of 73 studies that met the inclusion criteria of our meta-analysis were included (see Fig. 1). All eligible studies were published between 2003 and 2017. Among these, 70 articles were
Discussion
According to a recent epidemiological investigation, gastric cancer is the fifth most common cancer, and the third leading cause of cancer-related mortality globally, which accounted for 6.8% new cancer cases and 8.8% cancer-related mortality worldwide [2]. So far, the exact pathogenic mechanism of gastric cancer is still poorly understood despite extensive investigations. However, it has become evident recently that immune-regulatory cytokines may play vital roles in the process of tumor
Conclusions
In conclusion, our study indicates that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 polymorphisms may serve as genetic biomarkers of gastric cancer in Asians. Further well-designed studies are still warranted to confirm our findings, and future investigations also need to explore the possible roles of other interleukin gene polymorphisms in gastric cancer.
Authors' contributions
Xingmu Wang and Feiying Yang conceived of the study, participated in its design. Xingmu Wang and Feiying Yang conducted the systematic literature review. Xingmu Wang, Feiying Yang and Guangen Xu performed data analyses. Xingmu Wang and Shuping Zhong drafted the manuscript. All authors have read and approved the final manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
For this type of study formal consent is not required.
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2021, GeneCitation Excerpt :Two SNPs in the IL family of immune response-related genes (IL-10 rs1800871 (Liu et al., 2018; Gao et al., 1990) and IL-8 rs4073 (Taguchi et al., 2005; Gao et al., 1990; Chang et al., 2017; Li et al., 2010; Ye et al., 2009) were also positively associated with AG risk. Previous meta-analysis reported that IL-10 rs1800871 was associated with the risk of gastric cancer, nasopharyngeal carcinoma, oral cancer, periodontitis and ulcerative colitis (Zou et al., 2014; Li et al., 2016; Wang et al., 2018), and enhanced the risk of gastric ulcer resulting from Hp infection (Ramis et al., 2017). IL-10, a multifunctional cytokine with anti-inflammatory property, could promote pro-inflammatory cytokine synthesis, enhance B cell production and facilitate its differentiation (Zou et al., 2014).
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These authors contributed equally to this work.