Quantitative assessment of the influence of tumor necrosis factor alpha polymorphism with gastritis and gastric cancer risk

Abstract

Tumor necrosis factor alpha (TNFA) is an important molecule in inflammatory, infectious, and tumoral processes. Inflammation is one of the early phases in the development of gastric cancer (GC). Therefore, several studies have examined the association of polymorphism in TNFA with gastritis and GC risk. A functional polymorphism, -308G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. To date, a number of studies have been carried out to investigate the relationship between the polymorphism and gastritis or GC susceptibility, but the results were conflicting. 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. An overall random-effects per-allele odds ratio of 1.16 (95 % confidence interval 1.04-1.29, P = 0.008) was found for the polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians, whereas no significant associations were found among East Asians and other ethnic populations. No associations between the polymorphism and gastritis were observed. In addition, our data indicate that TNFA is involved in GC susceptibility and confers its effect primarily in diffuse type of tumors. Besides, -308G>A polymorphism was found to be significantly associated with both cardiac and noncardiac tumors. This meta-analysis demonstrated that the TNFA -308G>A polymorphism is a risk factor for developing GC, but the associations vary in different ethnic populations.

Role of TNF-α -308G/A gene polymorphism in gastric cancer risk: A case control study and meta-analysis

“…Overall, the analysis showed subjects with the minor allele (A) or homozygous mutation (AA) had a 1.17 and 1.36 fold higher chance of development of GC, respectively. These observations are consistent with earlier meta-analyses (46,47). In addition, we observed an association between TNF-α polymorphisms with GC susceptibility in Caucasians but not in Asian ethnic groups, indicating a race-specific link between TNF-α -308G>A and GC susceptibility.…”

“…Earlier meta-analyses by two different group also reported similar observations in the year 2014 (46,49). In addition, several reports including only Caucasian ethnic group for analysis demonstrated a possible association with GC susceptibility, further strengthening our observations (50)(51)(52).…”

“…Our present meta-analysis has several advantages over previous reports. The most recent meta-analyses were reported in the year 2014 (46,49,51). In the present study, five recent case-control studies investigating the role of TNF-α -308G>A in GC susceptibility were included, leading to an analysis including a much larger number of cases (n=8353) and controls (n=12099) (13,14,16,28,29).…”

Single Nucleotide Polymorphisms in TNF are Associated with Susceptibility to Aspirin-exacerbated Respiratory Disease but not to Cytokine Levels: a Study in Mexican Mestizo Population

“…At the functional level, it has been reported that the A allele of rs1800629 increases the transcriptional rate of the gene [10,23,24]; additionally, this same polymorphism has been associated with different diseases, such as hepatic cirrhosis [25], gastritis, gastric cancer [26], Type 2 diabetes mellitus [27] and inflammatory-autoimmune diseases, such as ankylosing spondylitis [28], systemic lupus erythematosus [29] and rheumatoid arthritis [30]. With regard to respiratory diseases, Kumar et al found an association between the same polymorphism and bronchial asthma in an Indian population [31].…”

Investigation on the association between IL-10 C819T gene polymorphisms and susceptibility to gastric cancer

“…However, the precise etiology of this cancer remains unclear. Many previous studies have reported that polymorphisms in inflammationrelated genes, such as tumor necrosis factor-alpha, toll-like receptors, and interleukins (IL), may be involved in the development of gastric cancer (Assis et al, 2014;Castaño-Rodríguez et al, 2014;Li et al, 2014;Qadri et al, 2014).…”