Meta-Analysis
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World J Gastroenterol. Dec 28, 2013; 19(48): 9461-9471
Published online Dec 28, 2013. doi: 10.3748/wjg.v19.i48.9461
TNF-α-308 polymorphism and risk of digestive system cancers: A meta-analysis
Xu-Feng Guo, Jun Wang, Shi-Jie Yu, Jia Song, Meng-Yao Ji, Zhuo Cao, Ji-Xiang Zhang, Jing Wang, Wei-Guo Dong
Xu-Feng Guo, Jun Wang, Shi-Jie Yu, Jia Song, Meng-Yao Ji, Zhuo Cao, Ji-Xiang Zhang, Jing Wang, Wei-Guo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
Author contributions: Guo XF and Wang J contributed equally to this work. Guo XF wrote the manuscript; Wang J conducted the analysis of pooled data; Yu SJ, Song J, Ji MY, Cao Z, Zhang JX and Wang J collected the literature; Dong WG revised the manuscript.
Correspondence to: Dr. Wei-Guo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, Hubei Province, China. dwg@whu.edu.cn
Telephone: +86-27-88041911 Fax: +86-27-88042292
Received: September 2, 2013
Revised: October 11, 2013
Accepted: November 2, 2013
Published online: December 28, 2013
Abstract

AIM: To evaluate the association between the tumour necrosis factor alpha-308 (TNF-α-308) gene polymorphism and the risk of digestive system cancers.

METHODS: All eligible case-control studies published up to December 2012 were identified by searching PubMed, Web of Science, Embase and China National Knowledge Internet without language restrictions. The risk of digestive system cancers associated with the TNF-α-308 polymorphism was estimated for each study using odds ratio (OR) together with its 95%CI, respectively. Cochrane Collaboration RevMan 5.1 was used to perform the analysis. A χ2-test-based Q statistic test and an I2 test were performed to assess the between-study heterogeneity. When the Q test was significant (P < 0.05) or I2 > 50%, the random effects model was used, otherwise the fixed effects model was used.

RESULTS: Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included. Overall, a significant association was found between the TNF-α-308 polymorphism and the risk of digestive system cancers [dominant model: OR = 1.23, 95%CI: 1.09-1.39, (G/A) vs (G/G): OR = 1.15, 95%CI: 1.02-1.28, (A/A) vs (G/G): OR = 1.44, 95%CI: 1.19-1.73, recessive model: OR = 1.38, 95%CI: 1.15-1.66]. Furthermore, when the analysis was stratified by ethnicity, similar results were observed in both the Asian and Caucasian populations, except for the dominant model and heterozygote comparisons in the Asian population [dominant model: OR = 1.24, 95%CI: 0.99-1.56, (G/A) vs (G/G): OR = 1.09, 95%CI: 0.96-1.24]. When the cancer type subgroups were examined, similar results were detected in gastric and hepatocellular carcinomas; however, no significant association was observed among other digestive system cancers.

CONCLUSION: The TNF-α-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas, but not colorectal, pancreatic, or oesophageal cancer, in the Asian population.

Keywords: Tumour necrosis factor alpha, rs1800629, Polymorphism, Digestive system cancer, Meta-analysis, Association

Core tip: Genetic polymorphisms contribute to the risk of human malignant tumours. Many studies have reported the relationship between the tumour necrosis factor alpha-308 (TNF-α-308) gene polymorphism and risk of digestive system cancers. However, the results of these studies are inconsistent and contradictory. In this meta-analysis, our results suggest that the TNF-α-308 polymorphism is significantly associated with the risk of gastric and hepatocellular carcinomas in the Asian population (dominant model: 95%CI: 1.02-1.34, P < 0.05 and 95%CI: 1.20-2.54, P < 0.05, respectively). This finding indicates that certain polymorphisms and mutations at TNF-α-308 may increase susceptibility to digestive system cancers.