Relationship between the polymorphism of tumor necrosis factor-α-308 G>A and susceptibility to inflammatory bowel diseases and colorectal cancer: a meta-analysis

Abstract

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-a-308 G4A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-a-308 G4A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-a-308 G4A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-a-308 G4A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-a and other cytokines, and the interaction with environmental factors, in future studies.

Tumor Necrosis Factor-α 238 G/A Polymorphism and Risk of Hepatocellular Carcinoma: Evidence from a Meta-analysis

“…As an important inflammatory factor, the polymorphisms in TNF-α gene have been largely studied, and TNF-α polymorphisms have been suggested to be associated with risks of many diseases, including rheumatoid arthritis, ankylosing spondylitis, and hepatitis B (Marcos et al, 2009;Postal et al, 2011). There are also many studies suggesting TNF-α polymorphisms are associated with risks of cancers, however, most them focus on the TNF-α -308 polymorphism (Fan et al, 2011;Wang et al, 2011). The relation between TNF-α -238 polymorphism and risk of cancer has not been well assessed.…”

“…There are several common single nucleotide polymorphisms (SNP) in the TNF-α gene, including −238 (rs361525), −308 (rs1800629), −857 (rs1799724), and −1031 (rs1799964) positions, which could regulate TNF-α transcription and production (Qidwai et al, 2011). It has been well demonstrated that those SNPs can affect the functions of relevant proteins and further influence the host susceptibility to various cancers (Fan et al, 2011;Wang et al, 2011). Many epidemiological studies have evaluated the association between TNF-α 238 G/A polymorphism and hepatocellular carcinoma risk (Heneghan et al, 2003;Wang et al, 2003;Niro et al, 2005;Jeng et al, 2007;Kummee et al, 2007;Jeng et al, 2009;Wang et al, 2010b;Chen et al, 2011).…”

Association between TNF-αrs1799724 and rs1800629 polymorphisms and the risk of Crohn’s disease

“…Environmental factors including smoking, appendectomy, or endogenous microbiota have also been implicated in the onset of CD (Mondot et al, 2011). Recent studies have shown inconsistent results regarding the role of the TNF-α rs1800629 G>A polymorphism in the pathophysiology of CD (Fan et al, 2011;López-Hernández et al, 2014). Therefore, this meta-analysis was conducted to examine the associations between the TNF-α rs1800629 G>A and TNF-α rs1799724 C>T polymorphisms and CD susceptibility.…”

“…Some studies suggest that the TNF-α rs1800629 G>A and TNF-α rs1799724 C>T polymorphisms are not involved in CD susceptibility (Xie et al, 2012;López-Hernández et al, 2014). However, another study found a strong association between the TNF-α rs1800629 G>A polymorphism and susceptibility to CD (Fan et al, 2011). In order to resolve these conflicting results, we conducted the present meta-analysis to investigate the role of the TNF-α rs1800629 G>A and TNF-α rs1799724 C>T polymorphisms in CD susceptibility.…”

“…TNF-α is secreted chiefly by activated macrophages, although it is also produced by many other cell types, including CD4+ lymphocytes, natural killer cells, neutrophils, mast cells, eosinophils, and neurons (Wynn et al, 2013). Particularly, TNF-α stimulates acute phase responses, resulting in elevated levels of C-reactive protein, interleukin-1 (IL-1), and prostaglandin E2 production (Fan et al, 2011). Abnormal TNF-α expression and secretion is observed in several human diseases, including Alzheimer's disease, cancers, major depressions, and IBD (Locksley et al, 2001).…”