Abstract
BackgroundTumor necrosis factor-α (TNF-α) plays a crucial role in the development and progression of gastric cancer. A functional polymorphism, -308 G>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. In the present study, we sought to investigate whether this polymorphism has effects on the risk and progression of gastric cancer in a Chinese population.MethodsWe genotyped the TNFA -308 G>A polymorphism using the TaqMan method in a two-stage case-control study comprising a total of 1686 gastric cancer patients and 1895 cancer-free subjects. The logistic regression was used to assess the genetic associations with occurrence and progression of gastric cancer.ResultsWe found a significant association between the variant genotypes and increased risk of gastric cancer [P = 0.034, odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.01–1.67, GA/AA vs. GG]. Similar results were observed in the follow-up replication study. When combined the data from the two studies, we found a more significant association (P = 0.001, OR = 1.34, 95%CI = 1.13–1.59), especially for older subjects (>65 years). Furthermore, the patients carrying the variant genotypes had a significantly greater prevalence of T4 stage of disease (P = 0.001, OR = 2.19, 95%CI = 1.39–3.47) and distant metastasis (P = 0.013, OR = 1.61, 95%CI = 1.10–2.35).ConclusionsOur results suggest that the functional promoter -308 G>A polymorphism in TNFA influence the susceptibility and progression of gastric cancer in the Chinese population.
Highlights
Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide, and prevalent in certain countries, including China [1,2]
A high prevalence of these risk factors do not always result in a high incidence of gastric cancer, which suggests that other susceptible factors such as genetic variations and environmental differences may contribute to gastric carcinogenesis
One of the important cytokines associated with H. pylori infection is the tumor necrosis factor (TNF) –a which is encoded by the TNFA gene [10]
Summary
Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related death worldwide, and prevalent in certain countries, including China [1,2]. A high prevalence of these risk factors do not always result in a high incidence of gastric cancer, which suggests that other susceptible factors such as genetic variations and environmental differences may contribute to gastric carcinogenesis. Emerging evidence has suggested that genetic polymorphisms in candidate genes were associated with susceptibility to gastric cancer [5,6,7]. Genetic variations in inflammation-related cytokine genes may be potential susceptibility factors for this disease. One of the important cytokines associated with H. pylori infection is the tumor necrosis factor (TNF) –a which is encoded by the TNFA gene [10]. Tumor necrosis factor-a (TNF-a) plays a crucial role in the development and progression of gastric cancer. We sought to investigate whether this polymorphism has effects on the risk and progression of gastric cancer in a Chinese population
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