Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis

Disease Markers, Dec 2016

Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study.

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Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis

Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis Ping Wang,1 June Wang,1,2 Mingxia Yu,1 and Zhiqiang Li3 1Department of Clinical Laboratory and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, China 2Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, China 3Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China Received 6 September 2016; Revised 4 December 2016; Accepted 6 December 2016 Academic Editor: Hubertus Himmerich Copyright © 2016 Ping Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study. 1. Introduction Cancer has been a disease which endangers human physical and psychosocial wellbeing, causing a significant public health and economic burden all over the world. Cancer is a multifactorial disease, and the etiology of these cancers is extremely complex. In order to understand its pathology, numerous susceptibility genes and external environmental factors appear to be considered. Chronic inflammation has long been associated with the development of cancer. Recent evidences have reignited the interest of cancer researchers in the exciting concept of an association between chronic inflammation and cancer. Rather than protecting against cancer, growing evidence indicates that TNF-α can promote the development of cancer [1]. Previously our study also found that targeting TNF-a suppressed breast cancer growth and TNF-α monoclonal antibody exerted effectively antitumor activity [2], which further supported this assertion. The length of TNF gene is 12 kilobases (kb) and it is located on the short arm of chromosome 6 (p21.1–p21.3) [3]. As transcription of TNF-α is regulated under genetic control, recent studies have shown that its promoter polymorphisms at TNF-α G-238A (rs361525), TNF-α G-308A (rs1800629), TNF-α T-857C (rs1799724), and TNF-α T-1031C (rs1799964) positions could regulate TNF-a production, thus affecting the risk of cancers [4–7]. Therefore, genetic polymorphisms of TNF-α gene have been supposed as candidate risk factors of cancer. There are a large number of studies on the association between TNF-α G-308A (rs1800629), TNF-α G-238A (rs361525), and cancers [8, 9]; TNF-α G-308A (rs1800629) and TNF-α G-238A (rs361525) have been successfully identified as risk factors of cancer. Molecular epidemiological research suggests that TNF-α T-857C (rs1799724) polymorphisms may be associated with an increased risk of cancers [10–13], but results remain controversial. TNF-α T-857C is a C to T transition in the promoter at position −857, and previous data have shown that TNF-α T-857C allele T increases the transcription of TNF-α [14–16]. Therefore, TNF-α T-857C polymorphism may be associated with cancer risk and represents candidate risk marker of cancers. To explore a more precise estimation of the relationship between TNF-α T-857C polymorphism and cancers, we performed a meta-analysis. 2. Materials and Methods2.1. Study Selection To identify eligible studies published before November 2015, we applied a systematic literature search strategy to the following electronic databases: PubMed/Medline, Embase, and Web of Science. We used the following keywords and subject headings in combination to identifying relevant articles in electr (...truncated)


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Ping Wang, June Wang, Mingxia Yu, Zhiqiang Li. Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis, Disease Markers, 2016, 2016, DOI: 10.1155/2016/4580323