The -308G/A Polymorphism of the Tumor Necrosis Factor-alpha Gene Is Associated with the Risk of Upper Aerodigestive Tract Cancer: A Meta-analysis

Abstract

Tumor necrosis factor-alpha (TNF-α ) has been proposed to contribute to the development of upper aerodigestive tract (UADT) cancer that is characterized by poor prognosis. The G-to-A nucleotide change at -308 of the TNF-α gene (-308G/A polymorphism) can increase the expression level of TNF-α and thus may affect the genetic susceptibility of UADT cancer. The association between the -308G/A polymorphism and UADT cancer has been widely studied, but the results published are quite controversial. To obtain a more precise conclusion, we performed a meta-analysis including 1,751 patients and 3,345 controls. The results indicated that the AA genotype of the -308G/A polymorphism had a 54%-increased risk of UADT cancer, compared with the G carriers (GG and GA genotypes) [odds ratio (OR) = 1.54, 95% confidence interval (CI): 1.07-2.21]. After stratified by ethnicity, the AA genotype was associated with increased risk of UADT cancers in South Asians (OR = 33.18 and 95% CI: 1.92-573.62 for AA vs. GA+GG) but not in Caucasians or East Asians. After stratified by tumor site, the -308G/A polymorphism was associated with increased risks of oropharynx cancer (OR = 2.68 and 95% CI: 1.34-5.35 for AA vs. GA+GG) but not associated with esophagus or larynx cancer. After stratified by histological type, the -308G/A polymorphism was associated with increased risks of squamous cell carcinoma (OR = 1.81 and 95% CI: 1.15-2.84 for AA vs. GA+GG) but not associated with adenocarcinoma. Our results indicate that the -308G/A polymorphism might contribute to an increased risk of UADT cancer susceptibility.

Genetic association between TNF-α promoter polymorphism and susceptibility to squamous cell carcinoma, basal cell carcinoma, and melanoma: A meta-analysis

“…We found that an increased overall SCC risk was associated with the rs1800629 polymorphisms in the Asian population under AA vs GG, and AA vs GG+GA models, but not A vs G, GA vs GG, GA+AA vs GG, or carrier A vs G models. A significant difference between LSCC/OSCC risks and the rs1800629 polymorphism was found under the AA vs GG, and AA vs GG+GA models; this corresponds with previous data on the link of rs1800629 and the risk of upper aero-digestive tract or head/neck SCC [ 25 , 26 ]. However, in 2013, Chen et al performed a meta-analysis to analyze the association between rs1800629 and oral cancer, and observed a negative association between rs1800629 and OSCC [ 27 ].…”

Tumor necrosis factor-α (TNF-α)-308G/A promoter polymorphism in colorectal cancer in ethnic Kashmiri population — A case control study in a detailed perspective

“…Several meta-analyses studies have shown a moderate to strong association of TNF-α-308G/A SNP with an increased risk of and in many cases the progression of various cancers including hepatocellular carcinoma ( Feng et al, 2014 , Hu et al, 2014 ), prostate cancer ( Ma et al, 2014 ), oral cancer ( Yapijakis et al, 2009 ), lung cancer ( Peng et al, 2012 , Shih et al, 2006 ), cervical cancer ( Pan et al, 2012 , Zhang and Zhang, 2013 ), gastric cancer ( Gorouhi et al, 2008 , Hong et al, 2013 , Lu et al, 2010 , Zhang et al, 2008 ), esophageal cancer ( Wang et al, 2013 ), breast cancer ( Wang et al, 2011 , Yang et al, 2011b ) and colorectal cancer ( Chen et al, 2013 , Min et al, 2014 ). At the protein level, high plasma levels of TNF-α has been found in cancer patients and these high plasma levels have been associated with a poor prognosis in various cancers ( Abrahamsson et al, 1993 , Nakashima et al, 1998 ) including CRC ( Balkwill, 2002 ).Various studies have demonstrated the role of TNF-α as a key player in the progression of human CRC ( Balkwill, 2002 , Sharma et al, 2008 ).…”

The Association between Hypoxia-Inducible Factor-1 α Gene C1772T Polymorphism and Cancer Risk: A Meta-Analysis of 37 Case-Control Studies

“…The methods used for literature search and data extraction has been described elsewhere [41]. In brief, With the term “(cancer or carcinoma) and (Hypoxia-inducible factor-1α or HIF-1α) and (Polymorphism or mutation or variant)”, we found 35 reference in the PubMed, Embase and China National Knowledge Infrastructure (CNKI) database that were published after the first report on HIF-1α(last update: August 23 2013).…”