High expression of tumor necrosis factor receptor-associated factor 2 promotes tumor metastasis and is associated with unfavorable prognosis in gastric cancer.
The study results revealed that IL-1β rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30-2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67-3.83) and TNF-αrs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54-3.46) polymorphisms significantly contributed toward GC risk.
In the subgroup analysis, we found that TNF-α-238G/A polymorphism was associated with the increased risk of GC amongst Asians, especially in Chinese, but not in Caucasians.
These results suggest that TNF-α-induced MMP-9 secretion from mesothelial cells plays an important role in the metastatic dissemination of gastric cancer.
A novel vascular-targeting peptide for gastric cancer delivers low-dose TNFα to normalize the blood vessels and improve the anti-cancer efficiency of 5-fluorouracil.
However, subtype-specific associations were observed for gastric cardia adenocarcinomas at MUC1/TRIM46/1q22 rs2070803 [HRAA versus GA+GG = 2.16; 95% confidence interval (CI) = 1.24-3.78; P = 0.0068] and LTA/TNF/6p21.33 rs1799724 (HRTT+CT versus CC = 1.30; 95% CI = 1.07-1.57; P = 0.0077), and for diffuse-type GC at PSCA/8q24.3 rs2294008 (HRTT versus CT+CC = 1.99; 95% CI = 1.33-2.97; P = 7.8E-04).
Our meta-analyses suggest that TNF-<i>α</i> T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development.
Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that plays a role in controlling the progression of lung cancer, hepatocellular cancer, breast cancer and gastric cancer.
The relative mRNA expression levels (RQ) of TNF-α, IL-8, and IL-10 were markedly downregulated in the CG group (median RQs = 0.128, 0.247, and 0.614, respectively), while the RQ levels of TNF-α in the GC group were upregulated (RQ = 2.749), but were basal for IL-8 (RQ = 1.053) and downregulated for IL-10 (RQ = 0.179).
Our study found that TNF-α expression may play a vital role in peritoneal metastasis of GC, while IL-1B expression might not be correlated with peritoneal metastasis.
To investigate this inconsistency, we performed a meta-analysis of 36 studies for TNFA -308G>A polymorphism to evaluate the effect of TNFA on genetic susceptibility for gastritis and GC.