Elsevier

Cytokine

Volume 111, November 2018, Pages 230-236
Cytokine

The roles of IL-6, IL-8 and IL-10 gene polymorphisms in gastric cancer: A meta-analysis

https://doi.org/10.1016/j.cyto.2018.08.024Get rights and content

Highlights

  • This is a comprehensive evidence-based meta-analysis on the roles of IL-6, IL-8 and IL-10 gene polymorphisms in GC.

  • Our findings indicate that the IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 polymorphisms may serve as genetic biomarkers of GC in Asians.

  • Our findings suggest that gene polymorphisms in immune regulators may contribute to the development of GC, and thus future studies are warranted to investigate the possible roles of other interleukin gene polymorphisms in GC.

Abstract

Background

Recently, the roles of interleukin-6 (IL-6), IL-8 and IL-10 gene polymorphisms in gastric cancer have been extensively studied, with conflicting results. Therefore, we conducted the present study to better assess the potential correlations between these interleukin gene polymorphisms and gastric cancer.

Methods

Eligible articles were searched in PubMed, Medline, Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between interleukin gene polymorphisms and the risk of gastric cancer.

Results

A total of 73 case-control studies were finally included. Significant associations with the risk of gastric cancer were only detected for the IL-8 rs4073 polymorphism in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that the IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 polymorphisms were all significantly associated with the risk of gastric cancer in Asians. No positive results were found for any investigated interleukin gene polymorphisms in Caucasians.

Conclusions

Our findings suggest 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.

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.

Section snippets

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.

References (19)

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These authors contributed equally to this work.

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